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Sample records for cochlear nucleus neurons

  1. Cochlear nucleus neuron analysis in individuals with presbycusis.

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    Hinojosa, Raul; Nelson, Erik G

    2011-12-01

    The aim of this study was to analyze the cochlear nucleus neuron population in individuals with normal hearing and presbycusis. Retrospective study of archival human temporal bone and brain stem tissues. Using strict inclusion criteria, the temporal bones and cochlear nuclei from six normal hearing individuals and four individuals with presbycusis were selected for analysis. The spiral ganglion cell population, the cochlear nucleus neuron population, and the cell body size of the neurons were quantified in these cases. A relationship was not observed between age and the spiral ganglion cell population in the normal hearing group. Presbycusis subjects exhibited a reduced spiral ganglion cell population. The mean cochlear nucleus neuron population was observed to be significantly higher in the presbycusis group (mean ± standard deviation: 114,170 ± 10,570) compared to the normal hearing group (91,470 ± 9,510) (P = .019). This difference was predominantly the result of greater multipolar and granule cell neuron populations. Only the fusiform neuron type exhibited a significantly different mean cell body cross-sectional area between the normal hearing group (242 ± 27) and the presbycusis group (300 ± 37) (P = .033). This investigation is the first time, to our knowledge, that the populations of the eight neuron types in the cochlear nucleus have been quantified in both normal hearing individuals and individuals with presbycusis. The data support the concept that presbycusis is not an effect of aging alone but instead may be a condition that predisposes one to hearing loss with advancing age and is characterized by a congenitally elevated cochlear nucleus neuron population. Copyright © 2011 The American Laryngological, Rhinological, and Otological Society, Inc.

  2. Auditory information coding by modeled cochlear nucleus neurons.

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    Wang, Huan; Isik, Michael; Borst, Alexander; Hemmert, Werner

    2011-06-01

    In this paper we use information theory to quantify the information in the output spike trains of modeled cochlear nucleus globular bushy cells (GBCs). GBCs are part of the sound localization pathway. They are known for their precise temporal processing, and they code amplitude modulations with high fidelity. Here we investigated the information transmission for a natural sound, a recorded vowel. We conclude that the maximum information transmission rate for a single neuron was close to 1,050 bits/s, which corresponds to a value of approximately 5.8 bits per spike. For quasi-periodic signals like voiced speech, the transmitted information saturated as word duration increased. In general, approximately 80% of the available information from the spike trains was transmitted within about 20 ms. Transmitted information for speech signals concentrated around formant frequency regions. The efficiency of neural coding was above 60% up to the highest temporal resolution we investigated (20 μs). The increase in transmitted information to that precision indicates that these neurons are able to code information with extremely high fidelity, which is required for sound localization. On the other hand, only 20% of the information was captured when the temporal resolution was reduced to 4 ms. As the temporal resolution of most speech recognition systems is limited to less than 10 ms, this massive information loss might be one of the reasons which are responsible for the lack of noise robustness of these systems.

  3. Sirt3 confers protection against acrolein-induced oxidative stress in cochlear nucleus neurons.

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    Qu, Juan; Wu, Yong-Xiang; Zhang, Ting; Qiu, Yang; Ding, Zhong-Jia; Zha, Ding-Jun

    2018-03-01

    Acrolein is a ubiquitous dietary and environmental pollutant, which can also be generated endogenously during cellular stress. However, the molecular mechanisms underlying acrolein-induced neurotoxicity, especially in ototoxicity conditions, have not been fully determined. In this study, we investigated the mechanisms on acrolein-induced toxicity in primary cultured cochlear nucleus neurons with focus on Sirt3, a mitochondrial deacetylase. We found that acrolein treatment induced neuronal injury and programmed cell death (PCD) in a dose dependent manner in cochlear nucleus neurons, which was accompanied by increased intracellular reactive oxygen species (ROS) generation and lipid peroxidation. Acrolein exposure also significantly reduced the mitochondrial membrane potential (MMP) levels, promoted cytochrome c release and decreased mitochondrial ATP production. In addition, increased ER tracker fluorescence and activation of ER stress factors were observed after acrolein treatment, and the ER stress inhibitors were shown to attenuate acrolein-induced toxicity in cochlear nucleus neurons. The results of western blot and RT-PCR showed that acrolein markedly decreased the expression of Sirt3 at both mRNA and protein levels, and reduced the activity of downstream mitochondrial enzymes. Furthermore, overexpression of Sirt3 by lentivirus transfection partially prevented acrolein-induced neuronal injury in cochlear nucleus neurons. These results demonstrated that acrolein induces mitochondrial dysfunction and ER stress in cochlear nucleus neurons, and Sirt3 acts as an endogenous protective factor in acrolein-induced ototoxicity. Copyright © 2017. Published by Elsevier Ltd.

  4. [Responses of bat cochlear nucleus neurons to ultrasonic stimuli].

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    Vasil'ev, A G; Grigor'eva, T I

    1977-01-01

    The responses of cochlear nuclei single units in Vespertilionidae and Rhinolophidae were studied by means of ultrasound stimuli of different frequencies. Most neurons were found to have one or two complementary response areas with best frequencies equal to 1/2 and 1/3 of the highest one (which we regard as the basic best frequency). In Vespertilionidae which emit frequency-modulated signals some neurons have complementary areas with upper thresholds. The latency of responses do not correlate with the stimulus frequency. This suggests that there is no correlative reception of echosignals at this level of auditory system in bats.

  5. Selective deletion of cochlear hair cells causes rapid age-dependent changes in spiral ganglion and cochlear nucleus neurons.

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    Tong, Ling; Strong, Melissa K; Kaur, Tejbeer; Juiz, Jose M; Oesterle, Elizabeth C; Hume, Clifford; Warchol, Mark E; Palmiter, Richard D; Rubel, Edwin W

    2015-05-20

    During nervous system development, critical periods are usually defined as early periods during which manipulations dramatically change neuronal structure or function, whereas the same manipulations in mature animals have little or no effect on the same property. Neurons in the ventral cochlear nucleus (CN) are dependent on excitatory afferent input for survival during a critical period of development. Cochlear removal in young mammals and birds results in rapid death of target neurons in the CN. Cochlear removal in older animals results in little or no neuron death. However, the extent to which hair-cell-specific afferent activity prevents neuronal death in the neonatal brain is unknown. We further explore this phenomenon using a new mouse model that allows temporal control of cochlear hair cell deletion. Hair cells express the human diphtheria toxin (DT) receptor behind the Pou4f3 promoter. Injections of DT resulted in nearly complete loss of organ of Corti hair cells within 1 week of injection regardless of the age of injection. Injection of DT did not influence surrounding supporting cells directly in the sensory epithelium or spiral ganglion neurons (SGNs). Loss of hair cells in neonates resulted in rapid and profound neuronal loss in the ventral CN, but not when hair cells were eliminated at a more mature age. In addition, normal survival of SGNs was dependent on hair cell integrity early in development and less so in mature animals. This defines a previously undocumented critical period for SGN survival. Copyright © 2015 the authors 0270-6474/15/357878-14$15.00/0.

  6. Development of chloride-mediated inhibition in neurons of the Anteroventral Cochlear Nucleus of Gerbil (Meriones unguiculatus).

    Czech Academy of Sciences Publication Activity Database

    Milenkovic, I.; Witte, M.; Tureček, Rostislav; Heinrich, M.; Reinert, T.; Rübsamen, R.

    2007-01-01

    Roč. 98, - (2007), s. 1634-1644 ISSN 0022-3077 R&D Projects: GA ČR GA309/03/1158; GA ČR GA309/06/1304 Institutional research plan: CEZ:AV0Z50390512 Keywords : Cochlear Nucleus * Neuron * Meriones unguiculatus Subject RIV: FH - Neurology Impact factor: 3.684, year: 2007

  7. Effect of cochlear nerve electrocautery on the adult cochlear nucleus.

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    Iseli, Claire E; Merwin, William H; Klatt-Cromwell, Cristine; Hutson, Kendall A; Ewend, Matthew G; Adunka, Oliver F; Fitzpatrick, Douglas C; Buchman, Craig A

    2015-04-01

    Electrocauterization and subsequent transection of the cochlear nerve induce greater injury to the cochlear nucleus than sharp transection alone. Some studies show that neurofibromatosis Type 2 (NF2) patients fit with auditory brainstem implants (ABIs) fail to achieve speech perception abilities similar to ABI recipients without NF2. Reasons for these differences remain speculative. One hypothesis posits poorer performance to surgically induced trauma to the cochlear nucleus from electrocautery. Sustained electrosurgical depolarization of the cochlear nerve may cause excitotoxic-induced postsynaptic nuclear injury. Equally plausible is that cautery in the vicinity of the cochlear nucleus induces necrosis. The cochlear nerve was transected in anesthetized adult gerbils sharply with or without bipolar electrocautery at varying intensities. Gerbils were perfused at 1, 3, 5, and 7 days postoperatively; their brainstem and cochleas were embedded in paraffin and sectioned at 10 μm. Alternate sections were stained with flourescent markers for neuronal injury or Nissl substance. In additional experiments, anterograde tracers were applied directly to a sectioned eighth nerve to verify that fluorescent-labeled profiles seen were terminating auditory nerve fibers. Cochlear nerve injury was observed from 72 hours postoperatively and was identical across cases regardless of surgical technique. Postsynaptic cochlear nucleus injury was not seen after distal transection of the nerve. By contrast, proximal transection was associated with trauma to the cochlear nucleus. Distal application of bipolar electrocautery seems safe for the cochlear nucleus. Application near the root entry zone must be used cautiously because this may compromise nuclear viability needed to support ABI stimulation.

  8. Serotonin projection patterns to the cochlear nucleus.

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    Thompson, A M; Thompson, G C

    2001-07-13

    The cochlear nucleus is well known as an obligatory relay center for primary auditory nerve fibers. Perhaps not so well known is the neural input to the cochlear nucleus from cells containing serotonin that reside near the midline in the midbrain raphe region. Although the specific locations of the main, if not sole, sources of serotonin within the dorsal cochlear nucleus subdivision are known to be the dorsal and median raphe nuclei, sources of serotonin located within other cochlear nucleus subdivisions are not currently known. Anterograde tract tracing was used to label fibers originating from the dorsal and median raphe nuclei while fluorescence immunohistochemistry was used to simultaneously label specific serotonin fibers in cat. Biotinylated dextran amine was injected into the dorsal and median raphe nuclei and was visualized with Texas Red, while serotonin was visualized with fluorescein. Thus, double-labeled fibers were unequivocally identified as serotoninergic and originating from one of the labeled neurons within the dorsal and median raphe nuclei. Double-labeled fiber segments, typically of fine caliber with oval varicosities, were observed in many areas of the cochlear nucleus. They were found in the molecular layer of the dorsal cochlear nucleus, in the small cell cap region, and in the granule cell and external regions of the cochlear nuclei, bilaterally, of all cats. However, the density of these double-labeled fiber segments varied considerably depending upon the exact region in which they were found. Fiber segments were most dense in the dorsal cochlear nucleus (especially in the molecular layer) and the large spherical cell area of the anteroventral cochlear nucleus; they were moderately dense in the small cell cap region; and fiber segments were least dense in the octopus and multipolar cell regions of the posteroventral cochlear nucleus. Because of the presence of labeled fiber segments in subdivisions of the cochlear nucleus other than the

  9. Ih equalizes membrane input resistance in a heterogeneous population of fusiform neurons in the dorsal cochlear nucleus.

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    Cesar Celis Ceballos

    2016-10-01

    Full Text Available In a neuronal population, several combinations of its ionic conductances are used to attain a specific firing phenotype. Some neurons present heterogeneity in their firing, generally produced by expression of a specific conductance, but how additional conductances vary along in order to homeostatically regulate membrane excitability is less known. Dorsal cochlear nucleus principal neurons, fusiform neurons, display heterogeneous spontaneous action potential activity and thus represent an appropriate model to study the role of different conductances in establishing firing heterogeneity. Particularly, fusiform neurons are divided into quiet, with no spontaneous firing, or active neurons, presenting spontaneous, regular firing. These modes are determined by the expression levels of an intrinsic membrane conductance, an inwardly rectifying potassium current (IKir. In this work, we tested whether other subthreshold conductances vary homeostatically to maintain membrane excitability constant across the two subtypes. We found that Ih expression covaries specifically with IKir in order to maintain membrane resistance constant. The impact of Ih on membrane resistance is dependent on the level of IKir expression, being much smaller in quiet neurons with bigger IKir, but Ih variations are not relevant for creating the quiet and active phenotypes. Finally, we demonstrate that the individual proportion of each conductance, and not their absolute conductance, is relevant for determining the neuronal firing mode. We conclude that in fusiform neurons the variations of their different subthreshold conductances are limited to specific conductances in order to create firing heterogeneity and maintain membrane homeostasis.

  10. In vivo analysis of the role of metabotropic glutamate receptors in the afferent regulation of chick cochlear nucleus neurons.

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    Carzoli, Kathryn L; Hyson, Richard L

    2011-02-01

    Cochlea removal results in the death of approximately 20-30% of neurons in the chick nucleus magnocellularis (NM). One early event in NM neuronal degradation is the disruption of their ribosomes. This can be visualized in the first few hours following cochlea removal using Y10B, an antibody that recognizes ribosomal RNA. Previous studies using a brain slice preparation suggest that maintenance of ribosomal integrity in NM neurons requires metabotropic glutamate receptor (mGluR) activation. Isolating the brain slice in vitro, however, may eliminate other potential sources of trophic support and only allows for evaluation of the early changes that occur in NM neurons following deafferentation. Consequently, it is not known if mGluR activation is truly required for the maintenance of NM neurons in the intact system. The current experiments evaluated the importance of mGluRs in vivo. The effects of short-term receptor blockade were assessed through Y10B labeling and the effects of long-term blockade were assessed through stereological counting of NM neurons in Nissl-stained tissue. mGluR antagonists or vehicle were administered intracerebroventricularly following unilateral cochlea removal. Vehicle-treated subjects replicated the previously reported effects of cochlea removal, showing lighter Y10B labeling and fewer Nissl-stained NM neurons on the deafened side of the brain. Blockade of mGluRs prevented the rapid activity-dependent difference in Y10B labeling, and in some cases, had the reverse effect, yielding lighter labeling of NM neurons on the intact side of the brain. Similarly, mGluR blockade over longer survival periods resulted in a reduction in number of cells on both intact and deafferented sides of the brain, and in some cases, yielded a reverse effect of fewer neurons on the intact side versus deafened side. These data are consistent with in vitro findings and suggest that mGluR activation plays a vital role in the afferent maintenance of NM neurons

  11. Dual Coding of Frequency Modulation in the Ventral Cochlear Nucleus.

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    Paraouty, Nihaad; Stasiak, Arkadiusz; Lorenzi, Christian; Varnet, Léo; Winter, Ian M

    2018-04-25

    Frequency modulation (FM) is a common acoustic feature of natural sounds and is known to play a role in robust sound source recognition. Auditory neurons show precise stimulus-synchronized discharge patterns that may be used for the representation of low-rate FM. However, it remains unclear whether this representation is based on synchronization to slow temporal envelope (ENV) cues resulting from cochlear filtering or phase locking to faster temporal fine structure (TFS) cues. To investigate the plausibility of those encoding schemes, single units of the ventral cochlear nucleus of guinea pigs of either sex were recorded in response to sine FM tones centered at the unit's best frequency (BF). The results show that, in contrast to high-BF units, for modulation depths within the receptive field, low-BF units (modulation depths extending beyond the receptive field, the discharge patterns follow the ENV and fluctuate at the modulation rate. The receptive field proved to be a good predictor of the ENV responses for most primary-like and chopper units. The current in vivo data also reveal a high level of diversity in responses across unit types. TFS cues are mainly conveyed by low-frequency and primary-like units and ENV cues by chopper and onset units. The diversity of responses exhibited by cochlear nucleus neurons provides a neural basis for a dual-coding scheme of FM in the brainstem based on both ENV and TFS cues. SIGNIFICANCE STATEMENT Natural sounds, including speech, convey informative temporal modulations in frequency. Understanding how the auditory system represents those frequency modulations (FM) has important implications as robust sound source recognition depends crucially on the reception of low-rate FM cues. Here, we recorded 115 single-unit responses from the ventral cochlear nucleus in response to FM and provide the first physiological evidence of a dual-coding mechanism of FM via synchronization to temporal envelope cues and phase locking to temporal

  12. Modeling of Auditory Neuron Response Thresholds with Cochlear Implants

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    Frederic Venail

    2015-01-01

    Full Text Available The quality of the prosthetic-neural interface is a critical point for cochlear implant efficiency. It depends not only on technical and anatomical factors such as electrode position into the cochlea (depth and scalar placement, electrode impedance, and distance between the electrode and the stimulated auditory neurons, but also on the number of functional auditory neurons. The efficiency of electrical stimulation can be assessed by the measurement of e-CAP in cochlear implant users. In the present study, we modeled the activation of auditory neurons in cochlear implant recipients (nucleus device. The electrical response, measured using auto-NRT (neural responses telemetry algorithm, has been analyzed using multivariate regression with cubic splines in order to take into account the variations of insertion depth of electrodes amongst subjects as well as the other technical and anatomical factors listed above. NRT thresholds depend on the electrode squared impedance (β = −0.11 ± 0.02, P<0.01, the scalar placement of the electrodes (β = −8.50 ± 1.97, P<0.01, and the depth of insertion calculated as the characteristic frequency of auditory neurons (CNF. Distribution of NRT residues according to CNF could provide a proxy of auditory neurons functioning in implanted cochleas.

  13. Medial Olivocochlear Reflex Interneurons Are Located in the Posteroventral Cochlear Nucleus: A Kainic Acid Lesion Study in Guinea Pigs

    OpenAIRE

    De VENECIA, RONALD K.; LIBERMAN, M. CHARLES; GUINAN, JOHN J.; BROWN, M. CHRISTIAN

    2005-01-01

    The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f1–f2)...

  14. Frequency-specific corticofugal modulation of the dorsal cochlear nucleus in mice.

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    Kong, Lingzhi; Xiong, Colin; Li, Liang; Yan, Jun

    2014-01-01

    The primary auditory cortex (AI) modulates the sound information processing in the lemniscal subcortical nuclei, including the anteroventral cochlear nucleus (AVCN), in a frequency-specific manner. The dorsal cochlear nucleus (DCN) is a non-lemniscal subcortical nucleus but it is tonotopically organized like the AVCN. However, it remains unclear how the AI modulates the sound information processing in the DCN. This study examined the impact of focal electrical stimulation of AI on the auditory responses of the DCN neurons in mice. We found that the electrical stimulation induced significant changes in the best frequency (BF) of DCN neurons. The changes in the BFs were highly specific to the BF differences between the stimulated AI neurons and the recorded DCN neurons. The DCN BFs shifted higher when the AI BFs were higher than the DCN BFs and the DCN BFs shifted lower when the AI BFs were lower than the DCN BFs. The DCN BFs showed no change when the AI and DCN BFs were similar. Moreover, the BF shifts were linearly correlated to the BF differences. Thus, our data suggest that corticofugal modulation of the DCN is also highly specific to frequency information, similar to the corticofugal modulation of the AVCN. The frequency-specificity of corticofugal modulation does not appear limited to the lemniscal ascending pathway.

  15. Retrograde transport of [3H]-D-aspartate label by cochlear and vestibular efferent neurons

    International Nuclear Information System (INIS)

    Schwarz, D.W.; Schwarz, I.E.

    1988-01-01

    [ 3 H]-D-aspartic acid was injected into the inner ear of rats. After a six hour survival time, labeled cells were found at all locations known to contain efferent cochlear or vestibular neurons. Most labeled neurons were found in the ipsilateral lateral superior olivary nucleus (LSO), although both ventral nuclei of the trapezoid body (VTB), group E, and the caudal pontine reticular nucleus (CPR) just adjacent to the ascending limb of the facial nerve also contained labeled cells. Because not all efferent neurons in the rat could be previously shown to be cholinergic, aspartate and glutamate are efferent transmitter candidates

  16. Coding of amplitude-modulated signals in the cochlear nucleus of a grass frog

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    Bibikov, N. G.

    2002-07-01

    To study the mechanisms that govern the coding of temporal features of complex sound signals, responses of single neurons located in the dorsal nucleus of the medulla oblongata (the cochlear nucleus) of a curarized grass frog ( Rana temporaria) to pure tone bursts and amplitude modulated tone bursts with a modulation frequency of 20 Hz and modulation depths of 10 and 80% were recorded. The carrier frequency was equal to the characteristic frequency of a neuron, the average signal level was 20 30 dB above the threshold, and the signal duration was equal to ten full modulation periods. Of the 133 neurons studied, 129 neurons responded to 80% modulated tone bursts by discharges that were phase-locked with the envelope waveform. At this modulation depth, the best phase locking was observed for neurons with the phasic type of response to tone bursts. For tonic neurons with low characteristic frequencies, along with the reproduction of the modulation, phase locking with the carrier frequency of the signal was observed. At 10% amplitude modulation, phasic neurons usually responded to only the onset of a tone burst. Almost all tonic units showed a tendency to reproduce the envelope, although the efficiency of the reproduction was low, and for half of these neurons, it was below the reliability limit. Some neurons exhibited a more efficient reproduction of the weak modulation. For almost half of the neurons, a reliable improvement was observed in the phase locking of the response during the tone burst presentation (from the first to the tenth modulation period). The cooperative histogram of a set of neurons responding to 10% modulated tone bursts within narrow ranges of frequencies and intensities retains the information on the dynamics of the envelope variation. The data are compared with the results obtained from the study of the responses to similar signals in the acoustic midbrain center of the same object and also with the psychophysical effect of a differential

  17. Synaptic reorganization in the adult rat's ventral cochlear nucleus following its total sensory deafferentation.

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    Heika Hildebrandt

    Full Text Available Ablation of a cochlea causes total sensory deafferentation of the cochlear nucleus in the brainstem, providing a model to investigate nervous degeneration and formation of new synaptic contacts in the adult brain. In a quantitative electron microscopical study on the plasticity of the central auditory system of the Wistar rat, we first determined what fraction of the total number of synaptic contact zones (SCZs in the anteroventral cochlear nucleus (AVCN is attributable to primary sensory innervation and how many synapses remain after total unilateral cochlear ablation. Second, we attempted to identify the potential for a deafferentation-dependent synaptogenesis. SCZs were ultrastructurally identified before and after deafferentation in tissue treated for ethanolic phosphotungstic acid (EPTA staining. This was combined with pre-embedding immunocytochemistry for gephyrin identifying inhibitory SCZs, the growth-associated protein GAP-43, glutamate, and choline acetyltransferase. A stereological analysis of EPTA stained sections revealed 1.11±0.09 (S.E.M.×10(9 SCZs per mm(3 of AVCN tissue. Within 7 days of deafferentation, this number was down by 46%. Excitatory and inhibitory synapses were differentially affected on the side of deafferentation. Excitatory synapses were quickly reduced and then began to increase in number again, necessarily being complemented from sources other than cochlear neurons, while inhibitory synapses were reduced more slowly and continuously. The result was a transient rise of the relative fraction of inhibitory synapses with a decline below original levels thereafter. Synaptogenesis was inferred by the emergence of morphologically immature SCZs that were consistently associated with GAP-43 immunoreactivity. SCZs of this type were estimated to make up a fraction of close to 30% of the total synaptic population present by ten weeks after sensory deafferentation. In conclusion, there appears to be a substantial potential

  18. Medial olivocochlear reflex interneurons are located in the posteroventral cochlear nucleus: a kainic acid lesion study in guinea pigs.

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    de Venecia, Ronald K; Liberman, M Charles; Guinan, John J; Brown, M Christian

    2005-07-11

    The medial olivocochlear (MOC) reflex arc is probably a three-neuron pathway consisting of type I spiral ganglion neurons, reflex interneurons in the cochlear nucleus, and MOC neurons that project to the outer hair cells of the cochlea. We investigated the identity of MOC reflex interneurons in the cochlear nucleus by assaying their regional distribution using focal injections of kainic acid. Our reflex metric was the amount of change in the distortion product otoacoustic emission (at 2f(1)-f(2)) just after onset of the primary tones. This metric for MOC reflex strength has been shown to depend on an intact reflex pathway. Lesions involving the posteroventral cochlear nucleus (PVCN), but not the other subdivisions, produced long-term decreases in MOC reflex strength. The degree of cell loss within the dorsal part of the PVCN was a predictor of whether the lesion affected MOC reflex strength. We suggest that multipolar cells within the PVCN have the distribution and response characteristics appropriate to be the MOC reflex interneurons. (c) 2005 Wiley-Liss, Inc.

  19. Central transport and distribution of labelled glutamic and aspartic acids to the cochlear nucleus in cats

    International Nuclear Information System (INIS)

    Kane, E.S.

    1979-01-01

    Tritiated L-glutamic acid or L-aspartic acid was injected unilaterally into the cochleas of adult cats, and 4 h-7 days later the localization of label was studied by light-microscopic autoradiography in sections of the brain stem. Consistent differences in labelling after glutamate and after aspartate suggest differences in their uptake, metabolic conversion and/or transport to the cochlear nucleus by cochlear fibers. The morphological differences shown here agree with the distribution of those two amino acids in the cat cochlear nucleus as shown by microchemical analyses. (author)

  20. Expression of immediate-early genes in the dorsal cochlear nucleus in salicylate-induced tinnitus.

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    Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

    2016-02-01

    Spontaneous neuronal activity in dorsal cochlear nucleus (DCN) may be involved in the physiological processes underlying salicylate-induced tinnitus. As a neuronal activity marker, immediate-early gene (IEG) expression, especially activity-dependent cytoskeletal protein (Arc/Arg3.1) and the early growth response gene-1 (Egr-1), appears to be highly correlated with sensory-evoked neuronal activity. However, their relationships with tinnitus induced by salicylate have rarely been reported in the DCN. In this study, we assessed the effect of acute and chronic salicylate treatment on the expression of N-methyl D-aspartate receptor subunit 2B (NR2B), Arg3.1, and Egr-1. We also observed ultrastructural alterations in the DCN synapses in an animal model of tinnitus. Levels of mRNA and protein expression of NR2B and Arg3.1 were increased in rats that were chronically administered salicylate (200 mg/kg, twice daily for 3, 7, or 14 days). These levels returned to baseline 14 days after cessation of treatment. However, no significant changes were observed in Egr-1 gene expression in any groups. Furthermore, rats subjected to long-term salicylate administration showed more presynaptic vesicles, thicker and longer postsynaptic densities, and increased synaptic interface curvature. Alterations of Arg3.1 and NR2B may be responsible for the changes in the synaptic ultrastructure. These changes confirm that salicylate can cause neural plasticity changes at the DCN level.

  1. Effects of brain-derived neurotrophic factor (BDNF) on the cochlear nucleus in cats deafened as neonates.

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    Kandathil, Cherian K; Stakhovskaya, Olga; Leake, Patricia A

    2016-12-01

    Many previous studies have shown significant neurotrophic effects of intracochlear delivery of BDNF in preventing degeneration of cochlear spiral ganglion (SG) neurons after deafness in rodents and our laboratory has shown similar results in developing cats deafened prior to hearing onset. This study examined the morphology of the cochlear nucleus (CN) in a group of neonatally deafened cats from a previous study in which infusion of BDNF elicited a significant improvement in survival of the SG neurons. Five cats were deafened by systemic injections of neomycin sulfate (60 mg/kg, SQ, SID) starting one day after birth, and continuing for 16-18 days until auditory brainstem response (ABR) testing demonstrated profound bilateral hearing loss. The animals were implanted unilaterally at about 1 month of age using custom-designed electrodes with a drug-delivery cannula connected to an osmotic pump. BDNF (94 μg/ml; 0.25 μl/hr) was delivered for 10 weeks. The animals were euthanized and studied at 14-23 weeks of age. Consistent with the neurotrophic effects of BDNF on SG survival, the total CN volume in these animals was significantly larger on the BDNF-treated side than on the contralateral side. However, total CN volume, both ipsi- and contralateral to the implants in these deafened juvenile animals, was markedly smaller than the CN in normal adult animals, reflecting the severe effects of deafness on the central auditory system during development. Data from the individual major CN subdivisions (DCN, Dorsal Cochlear Nucleus; PVCN, Posteroventral Cochlear Nucleus; AVCN, Anteroventral Cochlear Nucleus) also were analyzed. A significant difference was observed between the BDNF-treated and control sides only in the AVCN. Measurements of the cross-sectional areas of spherical cells showed that cells were significantly larger in the AVCN ipsilateral to the implant than on the contralateral side. Further, the numerical density of spherical cells was significantly lower in

  2. European multi-centre study of the Nucleus Hybrid L24 cochlear implant

    NARCIS (Netherlands)

    Lenarz, T.; James, C.; Cuda, D.; Fitzgerald O'Connor, A.; Frachet, B.; Frijns, J.H.M.; Klenzner, T.; Laszig, R.; Manrique, M.; Marx, M.; Merkus, P.; Mylanus, E.A.M.; Offeciers, E.; Pesch, J.; Ramos-Macias, A.; Robier, A.; Sterkers, O.; Uziel, A.

    2013-01-01

    Objectives: To investigate the preservation of residual hearing in subjects who received the Nucleus Hybrid L24 cochlear implant. To investigate the performance benefits up to one year post-implantation in terms of speech recognition, sound quality, and quality of life. Design: Prospective, with

  3. Medial Auditory Thalamus Is Necessary for Acquisition and Retention of Eyeblink Conditioning to Cochlear Nucleus Stimulation

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    Halverson, Hunter E.; Poremba, Amy; Freeman, John H.

    2015-01-01

    Associative learning tasks commonly involve an auditory stimulus, which must be projected through the auditory system to the sites of memory induction for learning to occur. The cochlear nucleus (CN) projection to the pontine nuclei has been posited as the necessary auditory pathway for cerebellar learning, including eyeblink conditioning.…

  4. Chronic tinnitus and unipolar brush cell alterations in the cerebellum and dorsal cochlear nucleus.

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    Brozoski, Thomas; Brozoski, Daniel; Wisner, Kurt; Bauer, Carol

    2017-07-01

    -Tinnitus). Neuron degeneration was also documented in the cochlear nucleus and PFL of exposed animals, both with and without tinnitus. Degeneration was not found in unexposed animals. Implications for tinnitus neuropathy are discussed in the context of synaptic remodeling and cerebellar sensory modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Central transport and distribution of labelled glutamic and aspartic acids to the cochlear nucleus in cats. An autoradiographic study

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    Kane, E S [University of Massachusetts Medical School, Worcester, MA (USA). Dept. of Anatomy

    1979-01-01

    Tritiated L-glutamic acid or L-aspartic acid was injected unilaterally into the cochleas of adult cats, and 4 h-7 days later the localization of label was studied by light-microscopic autoradiography in sections of the brain stem. Consistent differences in labelling after glutamate and after aspartate suggest differences in their uptake, metabolic conversion and/or transport to the cochlear nucleus by cochlear fibers. The morphological differences shown here agree with the distribution of those two amino acids in the cat cochlear nucleus as shown by microchemical analyses.

  6. Comparing Realistic Subthalamic Nucleus Neuron Models

    Science.gov (United States)

    Njap, Felix; Claussen, Jens C.; Moser, Andreas; Hofmann, Ulrich G.

    2011-06-01

    The mechanism of action of clinically effective electrical high frequency stimulation is still under debate. However, recent evidence points at the specific activation of GABA-ergic ion channels. Using a computational approach, we analyze temporal properties of the spike trains emitted by biologically realistic neurons of the subthalamic nucleus (STN) as a function of GABA-ergic synaptic input conductances. Our contribution is based on a model proposed by Rubin and Terman and exhibits a wide variety of different firing patterns, silent, low spiking, moderate spiking and intense spiking activity. We observed that most of the cells in our network turn to silent mode when we increase the GABAA input conductance above the threshold of 3.75 mS/cm2. On the other hand, insignificant changes in firing activity are observed when the input conductance is low or close to zero. We thus reproduce Rubin's model with vanishing synaptic conductances. To quantitatively compare spike trains from the original model with the modified model at different conductance levels, we apply four different (dis)similarity measures between them. We observe that Mahalanobis distance, Victor-Purpura metric, and Interspike Interval distribution are sensitive to different firing regimes, whereas Mutual Information seems undiscriminative for these functional changes.

  7. Activity patterns of cochlear ganglion neurones in the starling.

    Science.gov (United States)

    Manley, G A; Gleich, O; Leppelsack, H J; Oeckinghaus, H

    1985-09-01

    Spontaneous activity and responses to simple tonal stimuli were studied in cochlear ganglion neurones of the starling. Both regular and irregular spontaneous activity were recorded. Non-auditory cells have their origin in the macula lagenae. Mean spontaneous rate for auditory cells (all irregularly spiking) was 45 spikes s-1. In half the units having characteristic frequencies (CFs) less than 1.5 kHz, time-interval histograms (TIHs) of spontaneous activity showed regularly-spaced peaks or 'preferred' intervals. The spacing of the peak intervals was, on average, 15% greater than the CF-period interval of the respective units. In TIH of lower-frequency cells without preferred intervals, the modal interval was also on average about 15% longer than the CF-period interval. Apparently, the resting oscillation frequency of these cells lies below their CF. Tuning curves (TCs) of neurones to short tone bursts show no systematic asymmetry as in mammals. Below CF 1 kHz, the low-frequency flanks of the TCs are, on average, steeper than the high-frequency flanks. Above CF 1 kHz, the reverse is true. The cochlear ganglion and nerve are tonotopically organized. Low-frequency fibres arise apically in the papilla basilaris and are found near non-auditory (lagenar) fibres. Discharge rates to short tones were monotonically related to sound pressure level. Saturation rates often exceeded 300 spikes s-1. 'On-off' responses and primary suppression of spontaneous activity were observed. A direct comparison of spontaneous activity and tuning-curve symmetry revealed that, apart from quantitative differences, fundamental qualitative differences exist between starling and guinea-pig primary afferents.

  8. Qualitative analysis neurons in the adult human dentate nucleus

    Directory of Open Access Journals (Sweden)

    Marić Dušica

    2012-01-01

    Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

  9. Bilateral cochlear implants in infants: a new approach--Nucleus Hybrid S12 project.

    Science.gov (United States)

    Gantz, Bruce J; Dunn, Camille C; Walker, Elizabeth A; Kenworthy, Maura; Van Voorst, Tanya; Tomblin, Bruce; Turner, Chris

    2010-10-01

    The purpose of this feasibility study was to evaluate whether the use of a shorter-length cochlear implant (10 mm) on one ear and a standard electrode (24 mm) on the contralateral ear is a viable bilateral option for children with profound bilateral sensorineural hearing loss. A secondary purpose of this study was to determine whether the ear with the shorter-length electrode performs similarly to the standard-length electrode. Our goal was to provide an option of electrical stimulation that theoretically might preserve the structures of the scala media and organ of Corti. The study is being conducted as a repeated-measure, single-subject experiment. University of Iowa-Department of Otolaryngology. Eight pediatric patients with profound bilateral sensorineural hearing loss between the ages of 12 and 24 months. Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in the contralateral ear. The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) parent questionnaire, Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children's Vowel tests will be used to evaluate speech perception and the Minnesota Child Development Inventory and Preschool Language Scales 3 test will be used to evaluate language growth. Preliminary results for 8 children have been collected before and after the operation using the IT-MAIS. All 3 children showed incremental improvements in their IT-MAIS scores overtime. Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children's Vowel word perception results indicated no difference between the individual ears for the 2 children tested. Performance compared with age-matched children implanted with standard bilateral cochlear implants showed similar results to the children implanted with Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in contralateral ears. The use of a shorter-length cochlear implant on one ear and a standard-length electrode on the

  10. Bilateral Cochlear Implants in Infants: A New Approach—Nucleus Hybrid S12 Project

    Science.gov (United States)

    Gantz, Bruce J.; Dunn, Camille C.; Walker, Elizabeth A.; Kenworthy, Maura; Van Voorst, Tanya; Tomblin, Bruce; Turner, Chris

    2010-01-01

    Objective The purpose of this feasibility study was to evaluate whether the use of a shorter-length cochlear implant (10 mm) on one ear and a standard electrode (24 mm) on the contralateral ear is a viable bilateral option for children with profound bilateral sensorineural hearing loss. A secondary purpose of this study was to determine whether the ear with the shorter-length electrode performs similarly to the standard-length electrode. Our goal was to provide an option of electrical stimulation that theoretically might preserve the structures of the scala media and organ of Corti. Study Design The study is being conducted as a repeated-measure, single-subject experiment. Setting University of Iowa—Department of Otolaryngology. Patients Eight pediatric patients with profound bilateral sensorineural hearing loss between the ages of 12 and 24 months. Interventions Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in the contralateral ear. Main Outcome Measures The Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) parent questionnaire, Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children’s Vowel tests will be used to evaluate speech perception and the Minnesota Child Development Inventory and Preschool Language Scales 3 test will be used to evaluate language growth. Results Preliminary results for 8 children have been collected before and after the operation using the IT-MAIS. All 3 children showed incremental improvements in their IT-MAIS scores overtime. Early Speech Perception, Glendonald Auditory Screening Procedure word test, and Children’s Vowel word perception results indicated no difference between the individual ears for the 2 children tested. Performance compared with age-matched children implanted with standard bilateral cochlear implants showed similar results to the children implanted with Nucleus Hybrid S12 10-mm electrode and a Nucleus Freedom implant in contralateral ears

  11. Cochlear spike synchronization and neuron coincidence detection model

    Science.gov (United States)

    Bader, Rolf

    2018-02-01

    Coincidence detection of a spike pattern fed from the cochlea into a single neuron is investigated using a physical Finite-Difference model of the cochlea and a physiologically motivated neuron model. Previous studies have shown experimental evidence of increased spike synchronization in the nucleus cochlearis and the trapezoid body [Joris et al., J. Neurophysiol. 71(3), 1022-1036 and 1037-1051 (1994)] and models show tone partial phase synchronization at the transition from mechanical waves on the basilar membrane into spike patterns [Ch. F. Babbs, J. Biophys. 2011, 435135]. Still the traveling speed of waves on the basilar membrane cause a frequency-dependent time delay of simultaneously incoming sound wavefronts up to 10 ms. The present model shows nearly perfect synchronization of multiple spike inputs as neuron outputs with interspike intervals (ISI) at the periodicity of the incoming sound for frequencies from about 30 to 300 Hz for two different amounts of afferent nerve fiber neuron inputs. Coincidence detection serves here as a fusion of multiple inputs into one single event enhancing pitch periodicity detection for low frequencies, impulse detection, or increased sound or speech intelligibility due to dereverberation.

  12. Isolation and culture of adult mouse vestibular nucleus neurons

    Science.gov (United States)

    Him, Aydın; Altuntaş, Serap; Öztürk, Gürkan; Erdoğan, Ender; Cengiz, Nureddin

    2017-12-19

    Background/aim: Isolated cell cultures are widely used to study neuronal properties due to their advantages. Although embryonic animals are preferred for culturing, their morphological or electrophysiological properties may not reflect adult neurons, which may be important in neurodegenerative diseases. This paper aims to develop a method for preparing isolated cell cultures of medial vestibular nucleus (MVN) from adult mice and describe its morphological and electrophysiological properties.Materials and methods: Vestibular nucleus neurons were mechanically and enzymatically isolated and cultured using a defined medium with known growth factors. Cell survival was measured with propidium iodide, and electrophysiological properties were investigated with current-clamp recording.Results: Vestibular neurons grew neurites in cultures, gaining adult-like morphological properties, and stayed viable for 3 days in culture. Adding bovine calf serum, nerve growth factor, or insulin-like growth factor into the culture medium enhanced neuronal viability. Current-clamp recording of the cultured neurons revealed tonic and phasic-type neurons with similar input resistance, resting membrane potential, action potential amplitude, and duration. Conclusion: Vestibular neurons from adult mice can be cultured, and regenerate axons in a medium containing appropriate growth factors. Culturing adult vestibular neurons provides a new method to study age-related pathologies of the vestibular system.

  13. Neuronal plasticity in the hedgehog supraoptic nucleus during hibernation.

    Science.gov (United States)

    Sanchez-Toscano, F; Caminero, A A; Machin, C; Abella, G

    1989-01-01

    The purpose of the present study was to identify processes of plasticity in the receptive field of neurosecretory neurons of the supraoptic nucleus during hibernation in the hedgehog, in order to correlate them with the increased neurosecretory activity observed in this nucleus during this annual period. Using the Rapid Golgi method, a quantitative study was conducted in the receptive field of bipolar and multipolar neurons (the main components of the nucleus). Results indicate a generalized increase in the following characteristics: (1) number of dendritic spines per millimeter along the dendritic shafts; (2) degree of branching in the dendritic field; and (3) dendritic density around the neuronal soma. These data demonstrate modification of the dendritic field in the supraoptic nucleus during hibernation, a change undoubtedly related to functional conditions. Since the observed changes affect structures such as dendritic spines which are directly related to the arrival of neural afferences, the discussion is centered on the types of stimuli which may be responsible for the observed processes.

  14. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  15. Modulating central gain in tinnitus: changes in nitric oxide synthase in the ventral cochlear nucleus.

    Science.gov (United States)

    Coomber, Ben; Kowalkowski, Victoria L; Berger, Joel I; Palmer, Alan Richard; Wallace, Mark Nelson

    2015-01-01

    A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators - components of neural signaling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO) - a free radical and potent neuromodulator in the mammalian brain - that regulates plasticity via both pre-synaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN). Here, we examined nitric oxide synthase (NOS) - the enzyme responsible for NO production - in the guinea pig VCN following acoustic trauma. NOS was present in most cell types - including spherical and globular bushy cells, small, medium, and large multipolar cells, and octopus cells - spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE) resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioral evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as 1 day after AOE and was also present in some animals at 3, 7, and 21 days after AOE. However, it was not until 8 weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise exposure.

  16. Semitone frequency mapping to improve music representation for nucleus cochlear implants

    Directory of Open Access Journals (Sweden)

    Omran Sherif

    2011-01-01

    Full Text Available Abstract The frequency-to-channel mapping for Cochlear implant (CI signal processors was originally designed to optimize speech perception and generally does not preserve the harmonic structure of music sounds. An algorithm aimed at restoring the harmonic relationship of frequency components based on semitone mapping is presented in this article. Two semitone (Smt based mappings in different frequency ranges were investigated. The first, Smt-LF, covers a range from 130 to 1502 Hz which encompasses the fundamental frequency of most musical instruments. The second, Smt-MF, covers a range from 440 to 5040 Hz, allocating frequency bands of sounds close to their characteristic tonotopical sites according to Greenwood's function. Smt-LF, in contrast, transposes the input frequencies onto locations with higher characteristic frequencies. A sequence of 36 synthetic complex tones (C3 to B5, each consisting of a fundamental and 4 harmonic overtones, was processed using the standard (Std, Smt-LF and Smt-MF mappings. The analysis of output signals showed that the harmonic structure between overtones of all complex tones was preserved using Smt mapping. Semitone mapping preserves the harmonic structure and may in turn improve music representation for Nucleus cochlear implants. The proposed semitone mappings incorporate the use of virtual channels to allow frequencies spanning three and a half octaves to be mapped to 43 stimulation channels. A pitch difference limen test was done with normal hearing subjects discriminating pairs of pure tones with different semitone intervals which were processed by a vocoder type simulator of CI sound processing. The results showed better performance with wider semitone intervals. However, no significant difference was found between 22 and 43 channels maps.

  17. Modulating central gain in tinnitus: Changes in nitric oxide synthase in the ventral cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Ben eCoomber

    2015-03-01

    Full Text Available A significant challenge in tinnitus research lies in explaining how acoustic insult leads to tinnitus in some individuals, but not others. One possibility is genetic variability in the expression and function of neuromodulators – components of neural signalling that alter the balance of excitation and inhibition in neural circuits. An example is nitric oxide (NO – a free radical and potent neuromodulator in the mammalian brain – that regulates plasticity via both presynaptic and postsynaptic mechanisms. Changes in NO have previously been implicated in tinnitus generation, specifically in the ventral cochlear nucleus (VCN. Here, we examined nitric oxide synthase (NOS – the enzyme responsible for NO production – in the guinea pig VCN following acoustic trauma. NOS was present in most cell types – including spherical and globular bushy cells, small, medium and large multipolar cells, and octopus cells – spanning the entire extent of the VCN. The staining pattern was symmetrical in control animals. Unilateral acoustic over-exposure (AOE resulted in marked asymmetries between ipsilateral and contralateral sides of the VCN in terms of the distribution of NOS across the cochlear nuclei in animals with behavioural evidence of tinnitus: fewer NOS-positive cells and a reduced level of NOS staining was present across the whole extent of the contralateral VCN, relative to the ipsilateral VCN. The asymmetric pattern of NOS-containing cells was observed as early as one day after AOE and was also present in some animals at 3, 7 and 21 days after AOE. However it was not until eight weeks after AOE, when tinnitus had developed, that asymmetries were significant overall, compared with control animals. Asymmetrical NOS expression was not correlated with shifts in the threshold hearing levels. Variability in NOS expression between animals may represent one underlying difference that can be linked to whether or not tinnitus develops after noise

  18. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus

    Directory of Open Access Journals (Sweden)

    Miloslav eSedlacek

    2014-07-01

    Full Text Available Feedforward inhibition represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs, principal neurons of the dorsal cochlear nucleus (DCN that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and feed-forward inhibition in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven feed-forward inhibition (FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of feed-forward inhibition had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  19. Cell-type specific short-term plasticity at auditory nerve synapses controls feed-forward inhibition in the dorsal cochlear nucleus.

    Science.gov (United States)

    Sedlacek, Miloslav; Brenowitz, Stephan D

    2014-01-01

    Feed-forward inhibition (FFI) represents a powerful mechanism by which control of the timing and fidelity of action potentials in local synaptic circuits of various brain regions is achieved. In the cochlear nucleus, the auditory nerve provides excitation to both principal neurons and inhibitory interneurons. Here, we investigated the synaptic circuit associated with fusiform cells (FCs), principal neurons of the dorsal cochlear nucleus (DCN) that receive excitation from auditory nerve fibers and inhibition from tuberculoventral cells (TVCs) on their basal dendrites in the deep layer of DCN. Despite the importance of these inputs in regulating fusiform cell firing behavior, the mechanisms determining the balance of excitation and FFI in this circuit are not well understood. Therefore, we examined the timing and plasticity of auditory nerve driven FFI onto FCs. We find that in some FCs, excitatory and inhibitory components of FFI had the same stimulation thresholds indicating they could be triggered by activation of the same fibers. In other FCs, excitation and inhibition exhibit different stimulus thresholds, suggesting FCs and TVCs might be activated by different sets of fibers. In addition, we find that during repetitive activation, synapses formed by the auditory nerve onto TVCs and FCs exhibit distinct modes of short-term plasticity. Feed-forward inhibitory post-synaptic currents (IPSCs) in FCs exhibit short-term depression because of prominent synaptic depression at the auditory nerve-TVC synapse. Depression of this feedforward inhibitory input causes a shift in the balance of fusiform cell synaptic input towards greater excitation and suggests that fusiform cell spike output will be enhanced by physiological patterns of auditory nerve activity.

  20. Factors Influencing Short-term Synaptic Plasticity in the Avian Cochlear Nucleus Magnocellularis

    Directory of Open Access Journals (Sweden)

    Jason Tait Sanchez Quinones

    2015-01-01

    Full Text Available Defined as reduced neural responses during high rates of activity, synaptic depression is a form of short-term plasticity important for the temporal filtering of sound. In the avian cochlear nucleus magnocellularis (NM, an auditory brainstem structure, mechanisms regulating short-term synaptic depression include pre-, post-, and extrasynaptic factors. Using varied paired-pulse stimulus intervals, we found that the time course of synaptic depression lasts up to four seconds at late-developing NM synapses. Synaptic depression was largely reliant on exogenous Ca 2+ -dependent probability of presynaptic neurotransmitter release, and to a lesser extent, on the desensitization of postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptor (AMPA-R. Interestingly, although extrasynaptic glutamate clearance did not play a significant role in regulating synaptic depression, blocking glutamate clearance at early-developing synapses altered synaptic dynamics, changing responses from depression to facilitation. These results suggest a developmental shift in the relative reliance on pre-, post-, and extrasynaptic factors in regulating short-term synaptic plasticity in NM.

  1. Nucleus Ambiguus Cholinergic Neurons Activated by Acupuncture: Relation to Enkephalin

    Science.gov (United States)

    Guo, Zhi-Ling; Li, Min; Longhurst, John C.

    2012-01-01

    Acupuncture regulates autonomic function. Our previous studies have shown that electroacupuncture (EA) at the Jianshi–Neiguan acupoints (P5–P6, underlying the median nerve) inhibits central sympathetic outflow and attenuates excitatory cardiovascular reflexes, in part, through an opioid mechanism. It is unknown if EA at these acupoints influences the parasympathetic system. Thus, using c-Fos expression, we examined activation of nucleus ambiguus (NAmb) neurons by EA, their relation to cholinergic (preganglionic parasympathetic) neurons and those containing enkephalin. To enhance detection of cell bodies containing enkephalin, colchicine (90–100 μg/kg) was administered into the subarachnoid space of cats 30 hr prior to EA or sham-operated controls for EA. Following bilateral barodenervation and cervical vagotomy, either EA for 30 min at P5–P6 acupoints or control stimulation (needle placement at P5–P6 without stimulation) was applied. While perikarya containing enkephalin were observed in some medullary nuclei (e.g., râphe), only enkephalin-containing neuronal processes were found in the NAmb. Compared to controls (n=4), more c-Fos immunoreactivity, located principally in close proximity to fibers containing enkephalin was noted in the NAmb of EA-treated cats (n=5; P<0.01). Moreover, neurons double-labeled with c-Fos and choline acetyltransferase in the NAmb were identified in EA-treated, but not the control animals. These data demonstrate for the first time that EA activates preganglionic parasympathetic neurons in the NAmb. Because of their close proximity, these EA-activated neurons likely interact with nerve fibers containing enkephalin. These results suggest that EA at the P5–P6 acupoints has the potential to influence parasympathetic outflow and cardiovascular function, likely through an enkephalinergic mechanism. PMID:22306033

  2. Deafferentation-Induced Redistribution of MMP-2, but Not of MMP-9, Depends on the Emergence of GAP-43 Positive Axons in the Adult Rat Cochlear Nucleus

    Directory of Open Access Journals (Sweden)

    Michaela Fredrich

    2011-01-01

    Full Text Available The matrix metalloproteinases MMP-9 and MMP-2, major modulators of the extracellular matrix (ECM, were changed in amount and distribution in the rat anteroventral cochlear nucleus (AVCN following its sensory deafferentation by cochlear ablation. To determine what causal relationships exist between the redistribution of MMP-9 and MMP-2 and deafferentation-induced reinnervation, kainic acid was stereotaxically injected into the ventral nucleus of the trapezoid body (VNTB prior to cochlear ablation, killing cells that deliver the growth associated protein 43 (GAP-43 into AVCN. Deafferentation-induced changes in the pattern of MMP-9 staining remained unaffected by VNTB lesions. By contrast, changes in the distribution of MMP-2 normally evoked by sensory deafferentation were reversed if GAP-43 positive axons were prevented to grow in AVCN. In conclusion, GAP-43-containing axons emerging in AVCN after cochlear ablation seem to be causal for the maintenance of MMP-2-mediated ECM remodeling.

  3. Evidence for a persistent sodium conductance in neurons from the nucleus prepositus hypoglossi

    DEFF Research Database (Denmark)

    Rekling, J C; Laursen, A M

    1989-01-01

    Intracellular recordings were made from 39 neurons in a slice preparation of the prepositus hypoglossi nucleus from guinea pigs. Morphological characteristics were confirmed by dying neurons with Lucifer yellow. The neurons were spontaneously active, firing in the range of 8-50 spikes/s. Spike...

  4. Speech understanding in background noise with the two-microphone adaptive beamformer BEAM in the Nucleus Freedom Cochlear Implant System.

    Science.gov (United States)

    Spriet, Ann; Van Deun, Lieselot; Eftaxiadis, Kyriaky; Laneau, Johan; Moonen, Marc; van Dijk, Bas; van Wieringen, Astrid; Wouters, Jan

    2007-02-01

    This paper evaluates the benefit of the two-microphone adaptive beamformer BEAM in the Nucleus Freedom cochlear implant (CI) system for speech understanding in background noise by CI users. A double-blind evaluation of the two-microphone adaptive beamformer BEAM and a hardware directional microphone was carried out with five adult Nucleus CI users. The test procedure consisted of a pre- and post-test in the lab and a 2-wk trial period at home. In the pre- and post-test, the speech reception threshold (SRT) with sentences and the percentage correct phoneme scores for CVC words were measured in quiet and background noise at different signal-to-noise ratios. Performance was assessed for two different noise configurations (with a single noise source and with three noise sources) and two different noise materials (stationary speech-weighted noise and multitalker babble). During the 2-wk trial period at home, the CI users evaluated the noise reduction performance in different listening conditions by means of the SSQ questionnaire. In addition to the perceptual evaluation, the noise reduction performance of the beamformer was measured physically as a function of the direction of the noise source. Significant improvements of both the SRT in noise (average improvement of 5-16 dB) and the percentage correct phoneme scores (average improvement of 10-41%) were observed with BEAM compared to the standard hardware directional microphone. In addition, the SSQ questionnaire and subjective evaluation in controlled and real-life scenarios suggested a possible preference for the beamformer in noisy environments. The evaluation demonstrates that the adaptive noise reduction algorithm BEAM in the Nucleus Freedom CI-system may significantly increase the speech perception by cochlear implantees in noisy listening conditions. This is the first monolateral (adaptive) noise reduction strategy actually implemented in a mainstream commercial CI.

  5. Effects of VPAC1 activation in nucleus ambiguus neurons.

    Science.gov (United States)

    Gherghina, Florin Liviu; Tica, Andrei Adrian; Deliu, Elena; Abood, Mary E; Brailoiu, G Cristina; Brailoiu, Eugen

    2017-02-15

    The pituitary adenylyl cyclase-activating polypeptide (PACAP) and its G protein-coupled receptors, PAC1, VPAC1 and VPAC2 form a system involved in a variety of biological processes. Although some sympathetic stimulatory effects of this system have been reported, its central cardiovascular regulatory properties are poorly characterized. VPAC1 receptors are expressed in the nucleus ambiguus (nAmb), a key center controlling cardiac parasympathetic tone. In this study, we report that selective VPAC1 activation in rhodamine-labeled cardiac vagal preganglionic neurons of the rat nAmb produces inositol 1,4,5-trisphosphate receptor-mediated Ca 2+ mobilization, membrane depolarization and activation of P/Q-type Ca 2+ channels. In vivo, this pathway converges onto transient reduction in heart rate of conscious rats. Therefore we demonstrate a VPAC1-dependent mechanism in the central parasympathetic regulation of the heart rate, adding to the complexity of PACAP-mediated cardiovascular modulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

    NARCIS (Netherlands)

    Cafarelli-Dees, D.; Dillier, N.; Lai, W.K.; Wallenberg, E. von; Dijk, B. van; Akdas, F.; Aksit, M.; Batman, C.; Beynon, A.J.; Burdo, S.; Chanal, J.M.; Collet, L.; Conway, M.; Coudert, C.; Craddock, L.; Cullington, H.; Deggouj, N.; Fraysse, B.; Grabel, S.; Kiefer, J.; Kiss, J.G.; Lenarz, T.; Mair, A.; Maune, S.; Muller-Deile, J.; Piron, J.P.; Razza, S.; Tasche, C.; Thai-Van, H.; Toth, F.; Truy, E.; Uziel, A.; Smoorenburg, G.F.

    2005-01-01

    One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement

  7. Decreased number of oxytocin neurons in the paraventricular nucleus of the human hypothalamus in AIDS

    NARCIS (Netherlands)

    Purba, J. S.; Hofman, M. A.; Portegies, P.; Troost, D.; Swaab, D. F.

    1993-01-01

    The number of immunocytochemically identified vasopressin (AVP) and oxytocin (OXT) neurons was determined morphometrically in the paraventricular nucleus of the hypothalamus of 20 acquired immunodeficiency syndrome (AIDS) patients and 10 controls. The AIDS group consisted of 14 homosexual males (age

  8. Glutamate co-transmission from developing medial nucleus of the trapezoid body - Lateral superior olive synapses is cochlear dependent in kanamycin-treated rats

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jae Ho [Institute of Tissue Regeneration Engineering (ITREN), Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Pradhan, Jonu [Department of Nanobio Medical Science, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Maskey, Dhiraj; Park, Ki Sup [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Hong, Sung Hwa [Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University, School of Medicine, 50, Irwon-dong, Gangnam-gu, Seoul 135-710 (Korea, Republic of); Suh, Myung-Whan [Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Kim, Myeung Ju, E-mail: mjukim99@dankook.ac.kr [Department of Anatomy, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of); Ahn, Seung Cheol, E-mail: ansil67@hanmail.net [Department of Physiology, College of Medicine, Dankook University, San 29, Anseo-dong, Cheonan-si, Chungnam 330-714 (Korea, Republic of)

    2011-02-11

    Research highlights: {yields} Glutamate co-transmission is enhanced in kanamycin-treated rats. {yields} VGLUT3 expression is increased in kanamycin-treated rats. {yields} GlyR expression is decreased in kanamycin-treated rats. {yields} GlyR, VGLUT3 expression patterns are asymmetric in unilaterally cochlear ablated rat. -- Abstract: Cochlear dependency of glutamate co-transmission at the medial nucleus of the trapezoid body (MNTB) - the lateral superior olive (LSO) synapses was investigated using developing rats treated with high dose kanamycin. Rats were treated with kanamycin from postnatal day (P) 3 to P8. A scanning electron microscopic study on P9 demonstrated partial cochlear hair cell damage. A whole cell voltage clamp experiment demonstrated the increased glutamatergic portion of postsynaptic currents (PSCs) elicited by MNTB stimulation in P9-P11 kanamycin-treated rats. The enhanced VGLUT3 immunoreactivities (IRs) in kanamycin-treated rats and asymmetric VGLUT3 IRs in the LSO of unilaterally cochlear ablated rats supported the electrophysiologic data. Taken together, it is concluded that glutamate co-transmission is cochlear-dependent and enhanced glutamate co-transmission in kanamycin-treated rats is induced by partial cochlear damage.

  9. Probing the Electrode–Neuron Interface With Focused Cochlear Implant Stimulation

    Science.gov (United States)

    Bierer, Julie Arenberg

    2010-01-01

    Cochlear implants are highly successful neural prostheses for persons with severe or profound hearing loss who gain little benefit from hearing aid amplification. Although implants are capable of providing important spectral and temporal cues for speech perception, performance on speech tests is variable across listeners. Psychophysical measures obtained from individual implant subjects can also be highly variable across implant channels. This review discusses evidence that such variability reflects deviations in the electrode–neuron interface, which refers to an implant channel's ability to effectively stimulate the auditory nerve. It is proposed that focused electrical stimulation is ideally suited to assess channel-to-channel irregularities in the electrode–neuron interface. In implant listeners, it is demonstrated that channels with relatively high thresholds, as measured with the tripolar configuration, exhibit broader psychophysical tuning curves and smaller dynamic ranges than channels with relatively low thresholds. Broader tuning implies that frequency-specific information intended for one population of neurons in the cochlea may activate more distant neurons, and a compressed dynamic range could make it more difficult to resolve intensity-based information, particularly in the presence of competing noise. Degradation of both types of cues would negatively affect speech perception. PMID:20724356

  10. Distinct subsets of nucleus basalis neurons exhibit similar sensitivity to excitotoxicity

    NARCIS (Netherlands)

    Harkany, Tibor; Varga, Csaba; Grosche, Jens; Mulder, Jan; Luiten, Paul G.M.; Hortobágyi, Tibor; Penke, Botond; Härtig, Wolfgang

    2002-01-01

    Excitotoxic lesions in the magnocellular nucleus basalis (MBN) lead to a significant damage of cholinergic neurons concomitant with increased amyloid precursor protein (APP) expression in the cerebral cortex. However, the sensitivity of non-cholinergic neurons to excitotoxicity, and changes of APP

  11. Activity of vasopressinergic neurones of the human supraoptic nucleus is age- and sex-dependent

    NARCIS (Netherlands)

    Ishunina, T. A.; Salehi, A.; Hofman, M. A.; Swaab, D. F.

    1999-01-01

    In the human hypothalamus, arginine-vasopressin (AVP) is produced for a major part by the neurones of the supraoptic nucleus (SON). Since plasma AVP levels in men were reported to be higher than those of women and we did not find a sex difference in the neurone number, a higher vasopressinergic

  12. Modeling the electrode-neuron interface of cochlear implants: effects of neural survival, electrode placement, and the partial tripolar configuration.

    Science.gov (United States)

    Goldwyn, Joshua H; Bierer, Steven M; Bierer, Julie Arenberg

    2010-09-01

    The partial tripolar electrode configuration is a relatively novel stimulation strategy that can generate more spatially focused electric fields than the commonly used monopolar configuration. Focused stimulation strategies should improve spectral resolution in cochlear implant users, but may also be more sensitive to local irregularities in the electrode-neuron interface. In this study, we develop a practical computer model of cochlear implant stimulation that can simulate neural activation in a simplified cochlear geometry and we relate the resulting patterns of neural activity to basic psychophysical measures. We examine how two types of local irregularities in the electrode-neuron interface, variations in spiral ganglion nerve density and electrode position within the scala tympani, affect the simulated neural activation patterns and how these patterns change with electrode configuration. The model shows that higher partial tripolar fractions activate more spatially restricted populations of neurons at all current levels and require higher current levels to excite a given number of neurons. We find that threshold levels are more sensitive at high partial tripolar fractions to both types of irregularities, but these effects are not independent. In particular, at close electrode-neuron distances, activation is typically more spatially localized which leads to a greater influence of neural dead regions. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  13. Cancer-induced anorexia and malaise are mediated by CGRP neurons in the parabrachial nucleus.

    Science.gov (United States)

    Campos, Carlos A; Bowen, Anna J; Han, Sung; Wisse, Brent E; Palmiter, Richard D; Schwartz, Michael W

    2017-07-01

    Anorexia is a common manifestation of chronic diseases, including cancer. Here we investigate the contribution to cancer anorexia made by calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) that transmit anorexic signals. We show that CGRP PBN neurons are activated in mice implanted with Lewis lung carcinoma cells. Inactivation of CGRP PBN neurons before tumor implantation prevents anorexia and loss of lean mass, and their inhibition after symptom onset reverses anorexia. CGRP PBN neurons are also activated in Apc min/+ mice, which develop intestinal cancer and lose weight despite the absence of reduced food intake. Inactivation of CGRP PBN neurons in Apc min/+ mice permits hyperphagia that counteracts weight loss, revealing a role for these neurons in a 'nonanorexic' cancer model. We also demonstrate that inactivation of CGRP PBN neurons prevents lethargy, anxiety and malaise associated with cancer. These findings establish CGRP PBN neurons as key mediators of cancer-induced appetite suppression and associated behavioral changes.

  14. From synapse to nucleus and back again--communication over distance within neurons.

    Science.gov (United States)

    Fainzilber, Mike; Budnik, Vivian; Segal, Rosalind A; Kreutz, Michael R

    2011-11-09

    How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties. Signaling complexes may be transported in endosomes, or as non-endosomal complexes associated with importins and dynein. Anterograde transport of RNA granules from the soma to neuronal processes, coupled with retrograde transport of proteins translated locally at terminals or within processes, may fuel ongoing bidirectional communication between soma and synapse to modulate synaptic plasticity as well as neuronal growth and survival decisions.

  15. Oxytocin-receptor-expressing neurons in the parabrachial nucleus regulate fluid intake.

    Science.gov (United States)

    Ryan, Philip J; Ross, Silvano I; Campos, Carlos A; Derkach, Victor A; Palmiter, Richard D

    2017-12-01

    Brain regions that regulate fluid satiation are not well characterized, yet are essential for understanding fluid homeostasis. We found that oxytocin-receptor-expressing neurons in the parabrachial nucleus of mice (Oxtr PBN neurons) are key regulators of fluid satiation. Chemogenetic activation of Oxtr PBN neurons robustly suppressed noncaloric fluid intake, but did not decrease food intake after fasting or salt intake following salt depletion; inactivation increased saline intake after dehydration and hypertonic saline injection. Under physiological conditions, Oxtr PBN neurons were activated by fluid satiation and hypertonic saline injection. Oxtr PBN neurons were directly innervated by oxytocin neurons in the paraventricular hypothalamus (Oxt PVH  neurons), which mildly attenuated fluid intake. Activation of neurons in the nucleus of the solitary tract substantially suppressed fluid intake and activated Oxtr PBN neurons. Our results suggest that Oxtr PBN neurons act as a key node in the fluid satiation neurocircuitry, which acts to decrease water and/or saline intake to prevent or attenuate hypervolemia and hypernatremia.

  16. Fine structure of long-term changes in the cochlear nucleus after acoustic overstimulation: chronic degeneration and new growth of synaptic endings.

    Science.gov (United States)

    Kim, J J; Gross, J; Potashner, S J; Morest, D K

    2004-09-15

    The companion study showed that acoustic overstimulation of adult chinchillas, with a noise level sufficient to damage the cochlea, led to cytological changes and degeneration of synaptic endings in the cochlear nucleus within 1-16 weeks. In the present study, the same stimulus was used to study the long-term effects on the fine structure of synaptic endings in the cochlear nucleus. For periods of 6 and 8 months after a single exposure to a damaging noise level, there ensued a chronic, continuing process of neurodegeneration involving excitatory and inhibitory synaptic endings. Electron microscopic observations demonstrated freshly occurring degeneration even as late as 8 months. Degeneration was widespread in the neuropil and included the synapses on the globular bushy cell, which forms part of the main ascending auditory pathway. Neurodegeneration was accompanied by newly formed synaptic endings, which repopulated some of the sites vacated previously by axosomatic endings on globular bushy cells. Many of these synaptic endings must arise from central interneurons. The findings suggest that overstimulation can induce a self-sustaining condition of progressive neurodegeneration accompanied by a new growth of synaptic endings. Noise-induced hearing loss thus may progress as a neurodegenerative disease with the capacity for synaptic reorganization within the cochlear nucleus.

  17. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    Science.gov (United States)

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  18. Neural Segregation of Concurrent Speech: Effects of Background Noise and Reverberation on Auditory Scene Analysis in the Ventral Cochlear Nucleus.

    Science.gov (United States)

    Sayles, Mark; Stasiak, Arkadiusz; Winter, Ian M

    2016-01-01

    Concurrent complex sounds (e.g., two voices speaking at once) are perceptually disentangled into separate "auditory objects". This neural processing often occurs in the presence of acoustic-signal distortions from noise and reverberation (e.g., in a busy restaurant). A difference in periodicity between sounds is a strong segregation cue under quiet, anechoic conditions. However, noise and reverberation exert differential effects on speech intelligibility under "cocktail-party" listening conditions. Previous neurophysiological studies have concentrated on understanding auditory scene analysis under ideal listening conditions. Here, we examine the effects of noise and reverberation on periodicity-based neural segregation of concurrent vowels /a/ and /i/, in the responses of single units in the guinea-pig ventral cochlear nucleus (VCN): the first processing station of the auditory brain stem. In line with human psychoacoustic data, we find reverberation significantly impairs segregation when vowels have an intonated pitch contour, but not when they are spoken on a monotone. In contrast, noise impairs segregation independent of intonation pattern. These results are informative for models of speech processing under ecologically valid listening conditions, where noise and reverberation abound.

  19. An Examination of Sources of Variability Across the Consonant-Nucleus-Consonant Test in Cochlear Implant Listeners

    Directory of Open Access Journals (Sweden)

    Julie Arenberg Bierer

    2016-04-01

    Full Text Available The 10 consonant-nucleus-consonant (CNC word lists are considered the gold standard in the testing of cochlear implant (CI users. However, variance in scores across lists could degrade the sensitivity and reliability of them to identify deficits in speech perception. This study examined the relationship between variability in performance among lists and the lexical characteristics of the words. Data are from 28 adult CI users. Each subject was tested on all 10 CNC word lists. Data were analyzed in terms of lexical characteristics, lexical frequency, neighborhood density, bi-, and tri-phonemic probabilities. To determine whether individual performance variability across lists can be reduced, the standard set of 10 phonetically balanced 50-word lists was redistributed into a new set of lists using two sampling strategies: (a balancing with respect to word lexical frequency or (b selecting words with equal probability. The mean performance on the CNC lists varied from 53.1% to 62.4% correct. The average difference between the highest and lowest scores within individuals across the lists was 20.9% (from 12% to 28%. Lexical frequency and bi-phonemic probabilities were correlated with word recognition performance. The range of scores was not significantly reduced for all individuals when responses were simulated with 1,000 sets of redistributed lists, using both types of sampling methods. These results indicate that resampling of words does not affect the test–retest reliability and diagnostic value of the CNC word test.

  20. Effects of salicylate on the inflammatory genes expression and synaptic ultrastructure in the cochlear nucleus of rats.

    Science.gov (United States)

    Hu, Shou-Sen; Mei, Ling; Chen, Jian-Yong; Huang, Zhi-Wu; Wu, Hao

    2014-04-01

    Aspirin (salicylate), as a common drug that is frequently used for long-term treatment in a clinical setting, has the potential to cause reversible tinnitus. However, few reports have examined the inflammatory cytokines expression and alteration of synaptic ultrastructure in the cochlear nucleus (CN) in a rat model of tinnitus. The tinnitus-like behavior of rats were detected by the gap prepulse inhibition of acoustic startle (GPIAS) paradigm. We investigated the expression levels of the tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), N-methyl D-aspartate receptor subunit 2A (NR2A) mRNA and protein in the CN and compared synapses ultrastructure in the CN of tinnitus rats with normal ones. GPIAS showed that rats with long-term administration of salicylate were experiencing tinnitus, and the mRNA and protein expression levels of TNF-α and NR2A were up-regulated in chronic treatment groups, and they returned to baseline 14 days after cessation of treatment. Furthermore, compared to normal rats, repetitive salicylate-treated rats showed a greater number of presynaptic vesicles, thicker and longer postsynaptic densities, increased synaptic interface curvature. These data revealed that chronic salicylate administration markedly, but reversibly, induces tinnitus possibly via augmentation of the expression of TNF-α and NR2A and cause changes in synaptic ultrastructure in the CN. Long-term administration of salicylate causes neural plasticity changes at the CN level.

  1. Comparison of speech perception performance between Sprint/Esprit 3G and Freedom processors in children implanted with nucleus cochlear implants.

    Science.gov (United States)

    Santarelli, Rosamaria; Magnavita, Vincenzo; De Filippi, Roberta; Ventura, Laura; Genovese, Elisabetta; Arslan, Edoardo

    2009-04-01

    To compare speech perception performance in children fitted with previous generation Nucleus sound processor, Sprint or Esprit 3G, and the Freedom, the most recently released system from the Cochlear Corporation that features a larger input dynamic range. Prospective intrasubject comparative study. University Medical Center. Seventeen prelingually deafened children who had received the Nucleus 24 cochlear implant and used the Sprint or Esprit 3G sound processor. Cochlear implantation with Cochlear device. Speech perception was evaluated at baseline (Sprint, n = 11; Esprit 3G, n = 6) and after 1 month's experience with the Freedom sound processor. Identification and recognition of disyllabic words and identification of vowels were performed via recorded voice in quiet (70 dB [A]), in the presence of background noise at various levels of signal-to-noise ratio (+10, +5, 0, -5) and at a soft presentation level (60 dB [A]). Consonant identification and recognition of disyllabic words, trisyllabic words, and sentences were evaluated in live voice. Frequency discrimination was measured in a subset of subjects (n = 5) by using an adaptive, 3-interval, 3-alternative, forced-choice procedure. Identification of disyllabic words administered at a soft presentation level showed a significant increase when switching to the Freedom compared with the previously worn processor in children using the Sprint or Esprit 3G. Identification and recognition of disyllabic words in the presence of background noise as well as consonant identification and sentence recognition increased significantly for the Freedom compared with the previously worn device only in children fitted with the Sprint. Frequency discrimination was significantly better when switching to the Freedom compared with the previously worn processor. Serial comparisons revealed that that speech perception performance evaluated in children aged 5 to 15 years was superior with the Freedom than previous generations of Nucleus

  2. Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning

    Directory of Open Access Journals (Sweden)

    Eugene V. Golanov

    2017-09-01

    Full Text Available Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1 hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS-injected animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as “diving response”.

  3. Neuronal Entropy-Rate Feature of Entopeduncular Nucleus in Rat Model of Parkinson's Disease.

    Science.gov (United States)

    Darbin, Olivier; Jin, Xingxing; Von Wrangel, Christof; Schwabe, Kerstin; Nambu, Atsushi; Naritoku, Dean K; Krauss, Joachim K; Alam, Mesbah

    2016-03-01

    The function of the nigro-striatal pathway on neuronal entropy in the basal ganglia (BG) output nucleus, i.e. the entopeduncular nucleus (EPN) was investigated in the unilaterally 6-hyroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease (PD). In both control subjects and subjects with 6-OHDA lesion of dopamine (DA) the nigro-striatal pathway, a histological hallmark for parkinsonism, neuronal entropy in EPN was maximal in neurons with firing rates ranging between 15 and 25 Hz. In 6-OHDA lesioned rats, neuronal entropy in the EPN was specifically higher in neurons with firing rates above 25 Hz. Our data establishes that the nigro-striatal pathway controls neuronal entropy in motor circuitry and that the parkinsonian condition is associated with abnormal relationship between firing rate and neuronal entropy in BG output nuclei. The neuronal firing rates and entropy relationship provide putative relevant electrophysiological information to investigate the sensory-motor processing in normal condition and conditions such as movement disorders.

  4. Distinct populations of neurons respond to emotional valence and arousal in the human subthalamic nucleus.

    Science.gov (United States)

    Sieger, Tomáš; Serranová, Tereza; Růžička, Filip; Vostatek, Pavel; Wild, Jiří; Štastná, Daniela; Bonnet, Cecilia; Novák, Daniel; Růžička, Evžen; Urgošík, Dušan; Jech, Robert

    2015-03-10

    Both animal studies and studies using deep brain stimulation in humans have demonstrated the involvement of the subthalamic nucleus (STN) in motivational and emotional processes; however, participation of this nucleus in processing human emotion has not been investigated directly at the single-neuron level. We analyzed the relationship between the neuronal firing from intraoperative microrecordings from the STN during affective picture presentation in patients with Parkinson's disease (PD) and the affective ratings of emotional valence and arousal performed subsequently. We observed that 17% of neurons responded to emotional valence and arousal of visual stimuli according to individual ratings. The activity of some neurons was related to emotional valence, whereas different neurons responded to arousal. In addition, 14% of neurons responded to visual stimuli. Our results suggest the existence of neurons involved in processing or transmission of visual and emotional information in the human STN, and provide evidence of separate processing of the affective dimensions of valence and arousal at the level of single neurons as well.

  5. An excitatory paraventricular nucleus to AgRP neuron circuit that drives hunger.

    Science.gov (United States)

    Krashes, Michael J; Shah, Bhavik P; Madara, Joseph C; Olson, David P; Strochlic, David E; Garfield, Alastair S; Vong, Linh; Pei, Hongjuan; Watabe-Uchida, Mitsuko; Uchida, Naoshige; Liberles, Stephen D; Lowell, Bradford B

    2014-03-13

    Hunger is a hard-wired motivational state essential for survival. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus (ARC) at the base of the hypothalamus are crucial to the control of hunger. They are activated by caloric deficiency and, when naturally or artificially stimulated, they potently induce intense hunger and subsequent food intake. Consistent with their obligatory role in regulating appetite, genetic ablation or chemogenetic inhibition of AgRP neurons decreases feeding. Excitatory input to AgRP neurons is important in caloric-deficiency-induced activation, and is notable for its remarkable degree of caloric-state-dependent synaptic plasticity. Despite the important role of excitatory input, its source(s) has been unknown. Here, through the use of Cre-recombinase-enabled, cell-specific neuron mapping techniques in mice, we have discovered strong excitatory drive that, unexpectedly, emanates from the hypothalamic paraventricular nucleus, specifically from subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cyclase-activating polypeptide (PACAP, also known as ADCYAP1). Chemogenetic stimulation of these afferent neurons in sated mice markedly activates AgRP neurons and induces intense feeding. Conversely, acute inhibition in mice with caloric-deficiency-induced hunger decreases feeding. Discovery of these afferent neurons capable of triggering hunger advances understanding of how this intense motivational state is regulated.

  6. Reactive neurogenesis and down-regulation of the potassium-chloride cotransporter KCC2 in the cochlear nuclei after cochlear deafferentation

    Directory of Open Access Journals (Sweden)

    Brahim Tighilet

    2016-08-01

    Full Text Available While many studies have been devoted to investigating the homeostatic plasticity triggered by cochlear hearing loss, the cellular and molecular mechanisms involved in these central changes remain elusive. In the present study, we investigated the possibility of reactive neurogenesis after unilateral cochlear nerve section in the cochlear nucleus of cats. We found a strong cell proliferation in all the cochlear nucleus sub-divisions ipsilateral to the lesion. Most of the newly generated cells survive up to one month after cochlear deafferentation in all cochlear nuclei (except the dorsal cochlear nucleus and give rise to a variety of cell types, i.e. microglial cells, astrocytes and neurons. Interestingly, many of the newborn neurons had an inhibitory (GABAergic phenotype. This result is intriguing since sensory deafferentation is usually accompanied by enhanced excitation, consistent with a reduction in central inhibition. The membrane potential effect of GABA depends, however, on the intra-cellular chloride concentration, which is maintained at low levels in adults by the potassium chloride co-transporter KCC2. The KCC2 density on the plasma membrane of neurons was then assessed after cochlear deafferentation in the cochlear nuclei ipsilateral and contralateral to the lesion. Cochlear deafferentation is accompanied by a strong down-regulation of KCC2 ipsilateral to the lesion at 3 and 30 days post-lesion. This study suggests that reactive neurogenesis and downregulation of KCC2 is part of the vast repertoire involved in homeostatic plasticity triggered by hearing loss. These central changes may also play a role in the generation of tinnitus and hyperacusis.

  7. Interactions between Brainstem Noradrenergic Neurons and the Nucleus Accumbens Shell in Modulating Memory for Emotionally Arousing Events

    Science.gov (United States)

    Kerfoot, Erin C.; Williams, Cedric L.

    2011-01-01

    The nucleus accumbens shell (NAC) receives axons containing dopamine-[beta]-hydroxylase that originate from brainstem neurons in the nucleus of the solitary tract (NTS). Recent findings show that memory enhancement produced by stimulating NTS neurons after learning may involve interactions with the NAC. However, it is unclear whether these…

  8. Paraventricular nucleus of the human hypothalamus in primary hypertension: Activation of corticotropin-releasing hormone neurons

    NARCIS (Netherlands)

    Goncharuk, Valeri D.; van Heerikhuize, Joop; Swaab, Dick F.; Buijs, Ruud M.

    2002-01-01

    By using quantitative immunohistochemical and in situ hybridization techniques, we studied corticotropin-releasing hormone (CRH)-producing neurons of the hypothalamic paraventricular nucleus (PVN) in patients who suffered from primary hypertension and died due to acute cardiac failure. The control

  9. Modulation of Hippocampal Theta Oscillations and Spatial Memory by Relaxin-3 Neurons of the Nucleus Incertus

    Science.gov (United States)

    Ma, Sherie; Olucha-Bordonau, Francisco E.; Hossain, M. Akhter; Lin, Feng; Kuei, Chester; Liu, Changlu; Wade, John D.; Sutton, Steven W.; Nunez, Angel; Gundlach, Andrew L.

    2009-01-01

    Hippocampal theta rhythm is thought to underlie learning and memory, and it is well established that "pacemaker" neurons in medial septum (MS) modulate theta activity. Recent studies in the rat demonstrated that brainstem-generated theta rhythm occurs through a multisynaptic pathway via the nucleus incertus (NI), which is the primary source of the…

  10. Astrocytes Control Neuronal Excitability in the Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Tommaso Fellin

    2007-01-01

    Full Text Available Though accumulating evidence shows that the metabotropic glutamate receptor 5 (mGluR5 mediates some of the actions of extracellular glutamate after cocaine use, the cellular events underlying this action are poorly understood. In this review, we will discuss recent results showing that mGluR5 receptors are key regulators of astrocyte activity. Synaptic release of glutamate activates mGluR5 expressed in perisynaptic astrocytes and generates intense Ca2+ signaling in these cells. Ca2+ oscillations, in turn, trigger the release from astrocytes of the gliotransmitter glutamate, which modulates neuronal excitability by activating NMDA receptors. By integrating these results with the most recent evidence demonstrating the importance of astrocytes in the regulation of neuronal excitability, we propose that astrocytes are involved in mediating some of the mGluR5-dependent drug-induced behaviors.

  11. Single-Cell Gene Expression Analysis of Cholinergic Neurons in the Arcuate Nucleus of the Hypothalamus.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    Full Text Available The cholinoceptive system in the hypothalamus, in particular in the arcuate nucleus (ARC, plays a role in regulating food intake. Neurons in the ARC contain multiple neuropeptides, amines, and neurotransmitters. To study molecular and neurochemical heterogeneity of ARC neurons, we combine single-cell qRT-PCR and single-cell whole transcriptome amplification methods to analyze expression patterns of our hand-picked 60 genes in individual neurons in the ARC. Immunohistochemical and single-cell qRT-PCR analyses show choline acetyltransferase (ChAT-expressing neurons in the ARC. Gene expression patterns are remarkably distinct in each individual cholinergic neuron. Two-thirds of cholinergic neurons express tyrosine hydroxylase (Th mRNA. A large subset of these Th-positive cholinergic neurons is GABAergic as they express the GABA synthesizing enzyme glutamate decarboxylase and vesicular GABA transporter transcripts. Some cholinergic neurons also express the vesicular glutamate transporter transcript gene. POMC and POMC-processing enzyme transcripts are found in a subpopulation of cholinergic neurons. Despite this heterogeneity, gene expression patterns in individual cholinergic cells appear to be highly regulated in a cell-specific manner. In fact, membrane receptor transcripts are clustered with their respective intracellular signaling and downstream targets. This novel population of cholinergic neurons may be part of the neural circuitries that detect homeostatic need for food and control the drive to eat.

  12. GHRELIN ACTIVATES HYPOPHYSIOTROPIC CORTICOTROPIN-RELEASING FACTOR NEURONS INDEPENDENTLY OF THE ARCUATE NUCLEUS

    Science.gov (United States)

    Cabral, Agustina; Portiansky, Enrique; Sánchez-Jaramillo, Edith; Zigman, Jeffrey M.; Perello, Mario

    2016-01-01

    Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin’s orexigenic action vs. its role as a stress signal are anatomically dissociated. PMID:26874559

  13. [Local GABA-ergic modulation of serotonergic neuron activity in the nucleus raphe magnus].

    Science.gov (United States)

    Iniushkin, A N; Merkulova, N A; Orlova, A O; Iniushkina, E M

    2009-07-01

    In voltage-clamp experimental on slices of the rat brainstem the effects of 5-HT and GABA on serotonergic neurons of nucleus raphe magnus were investigated. Local applications of 5-HT induced an increase in IPCSs frequency and amplitude in 45% of serotonergic cells. The effect suppressed by the blocker of fast sodium channels tetradotoxin. Antagonist of GABA receptor gabazine blocked IPSCs in neurons both sensitive and non-sensitive to 5-HT action. Applications of GABA induced a membrane current (I(GABA)), which was completely blocked by gabazine. The data suggest self-control of the activity of serotonergic neurons in nucleus raphe magnus by negative feedback loop via local GABAergic interneurons.

  14. The Edinger-Westphal nucleus of the juvenile rat contains transient- and repetitive-firing neurons

    DEFF Research Database (Denmark)

    Laursen, M; Rekling, J C

    2006-01-01

    Classically, the Edinger-Westphal nucleus is described as containing neurons controlling accommodation and pupillary constriction via projections to the ciliary ganglion. However, in several species including rat, some Edinger-Westphal neurons have ascending or descending CNS projections suggesting...... an immunohistochemical procedure directed at the peptide Urocortin, which is expressed in Edinger-Westphal neurons. Passive and active membrane responses were investigated and two different neuron types were identified. One type had a transient firing response to 400 ms depolarizing current pulses and one type had...... threshold Ca(2+) spikes were seen and these were blocked by nickel(II) chloride hexahydrate, suggesting that they are mediated via low voltage-activated Ca(2+) channels. Some biocytin-labeled neurons had axons or axonal collaterals projecting laterally or dorsally, suggesting possible non-ocular targets...

  15. Neurons within the trigeminal mesencephalic nucleus encode for the kinematic parameters of the whisker pad macrovibrissae.

    Science.gov (United States)

    Mameli, Ombretta; Caria, Marcello A; Biagi, Francesca; Zedda, Marco; Farina, Vittorio

    2017-05-01

    It has been recently shown in rats that spontaneous movements of whisker pad macrovibrissae elicited evoked responses in the trigeminal mesencephalic nucleus (Me5). In the present study, electrophysiological and neuroanatomical experiments were performed in anesthetized rats to evaluate whether, besides the whisker displacement per se, the Me5 neurons are also involved in encoding the kinematic properties of macrovibrissae movements, and also whether, as reported for the trigeminal ganglion, even within the Me5 nucleus exists a neuroanatomical representation of the whisker pad macrovibrissae. Extracellular electrical activity of single Me5 neurons was recorded before, during, and after mechanical deflection of the ipsilateral whisker pad macrovibrissae in different directions, and with different velocities and amplitudes. In several groups of animals, single or multiple injections of the tracer Dil were performed into the whisker pad of one side, in close proximity to the vibrissae follicles, in order to label the peripheral terminals of the Me5 neurons innervating the macrovibrissae (whisking-neurons), and therefore, the respective perikaria within the nucleus. Results showed that: (1) the whisker pad macrovibrissae were represented in the medial-caudal part of the Me5 nucleus by a single cluster of cells whose number seemed to match that of the macrovibrissae; (2) macrovibrissae mechanical deflection elicited significant responses in the Me5 whisking-neurons, which were related to the direction, amplitude, and frequency of the applied deflection. The specific functional role of Me5 neurons involved in encoding proprioceptive information arising from the macrovibrissae movements is discussed within the framework of the whole trigeminal nuclei activities. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  16. Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability.

    Science.gov (United States)

    Ziminski, Joseph J; Hessler, Sabine; Margetts-Smith, Gabriella; Sieburg, Meike C; Crombag, Hans S; Koya, Eisuke

    2017-03-22

    Cues that predict the availability of food rewards influence motivational states and elicit food-seeking behaviors. If a cue no longer predicts food availability, then animals may adapt accordingly by inhibiting food-seeking responses. Sparsely activated sets of neurons, coined "neuronal ensembles," have been shown to encode the strength of reward-cue associations. Although alterations in intrinsic excitability have been shown to underlie many learning and memory processes, little is known about these properties specifically on cue-activated neuronal ensembles. We examined the activation patterns of cue-activated orbitofrontal cortex (OFC) and nucleus accumbens (NAc) shell ensembles using wild-type and Fos-GFP mice, which express green fluorescent protein (GFP) in activated neurons, after appetitive conditioning with sucrose and extinction learning. We also investigated the neuronal excitability of recently activated, GFP+ neurons in these brain areas using whole-cell electrophysiology in brain slices. Exposure to a sucrose cue elicited activation of neurons in both the NAc shell and OFC. In the NAc shell, but not the OFC, these activated GFP+ neurons were more excitable than surrounding GFP- neurons. After extinction, the number of neurons activated in both areas was reduced and activated ensembles in neither area exhibited altered excitability. These data suggest that learning-induced alterations in the intrinsic excitability of neuronal ensembles is regulated dynamically across different brain areas. Furthermore, we show that changes in associative strength modulate the excitability profile of activated ensembles in the NAc shell. SIGNIFICANCE STATEMENT Sparsely distributed sets of neurons called "neuronal ensembles" encode learned associations about food and cues predictive of its availability. Widespread changes in neuronal excitability have been observed in limbic brain areas after associative learning, but little is known about the excitability changes that

  17. Clonidine, an α2 receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus

    OpenAIRE

    Philbin, Kerry E.; Bateman, Ryan J.; Mendelowitz, David

    2010-01-01

    In hypertension there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Pre-sympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these pre-sympathetic neurons are catecholaminergic. In addition to their projection to the spina...

  18. Wnt1 from cochlear schwann cells enhances neuronal differentiation of transplanted neural stem cells in a rat spiral ganglion neuron degeneration model.

    Science.gov (United States)

    He, Ya; Zhang, Peng-Zhi; Sun, Dong; Mi, Wen-Juan; Zhang, Xin-Yi; Cui, Yong; Jiang, Xing-Wang; Mao, Xiao-Bo; Qiu, Jian-Hua

    2014-04-01

    Although neural stem cell (NSC) transplantation is widely expected to become a therapy for nervous system degenerative diseases and injuries, the low neuronal differentiation rate of NSCs transplanted into the inner ear is a major obstacle for the successful treatment of spiral ganglion neuron (SGN) degeneration. In this study, we validated whether the local microenvironment influences the neuronal differentiation of transplanted NSCs in the inner ear. Using a rat SGN degeneration model, we demonstrated that transplanted NSCs were more likely to differentiate into microtubule-associated protein 2 (MAP2)-positive neurons in SGN-degenerated cochleae than in control cochleae. Using real-time quantitative PCR and an immunofluorescence assay, we also proved that the expression of Wnt1 (a ligand of Wnt signaling) increases significantly in Schwann cells in the SGN-degenerated cochlea. We further verified that NSC cultures express receptors and signaling components for Wnts. Based on these expression patterns, we hypothesized that Schwann cell-derived Wnt1 and Wnt signaling might be involved in the regulation of the neuronal differentiation of transplanted NSCs. We verified our hypothesis in vitro using a coculture system. We transduced a lentiviral vector expressing Wnt1 into cochlear Schwann cell cultures and cocultured them with NSC cultures. The coculture with Wnt1-expressing Schwann cells resulted in a significant increase in the percentage of NSCs that differentiated into MAP2-positive neurons, whereas this differentiation-enhancing effect was prevented by Dkk1 (an inhibitor of the Wnt signaling pathway). These results suggested that Wnt1 derived from cochlear Schwann cells enhanced the neuronal differentiation of transplanted NSCs through Wnt signaling pathway activation. Alterations of the microenvironment deserve detailed investigation because they may help us to conceive effective strategies to overcome the barrier of the low differentiation rate of transplanted

  19. Development of on-off spiking in superior paraolivary nucleus neurons of the mouse

    Science.gov (United States)

    Felix, Richard A.; Vonderschen, Katrin; Berrebi, Albert S.

    2013-01-01

    The superior paraolivary nucleus (SPON) is a prominent cell group in the auditory brain stem that has been increasingly implicated in representing temporal sound structure. Although SPON neurons selectively respond to acoustic signals important for sound periodicity, the underlying physiological specializations enabling these responses are poorly understood. We used in vitro and in vivo recordings to investigate how SPON neurons develop intrinsic cellular properties that make them well suited for encoding temporal sound features. In addition to their hallmark rebound spiking at the stimulus offset, SPON neurons were characterized by spiking patterns termed onset, adapting, and burst in response to depolarizing stimuli in vitro. Cells with burst spiking had some morphological differences compared with other SPON neurons and were localized to the dorsolateral region of the nucleus. Both membrane and spiking properties underwent strong developmental regulation, becoming more temporally precise with age for both onset and offset spiking. Single-unit recordings obtained in young mice demonstrated that SPON neurons respond with temporally precise onset spiking upon tone stimulation in vivo, in addition to the typical offset spiking. Taken together, the results of the present study demonstrate that SPON neurons develop sharp on-off spiking, which may confer sensitivity to sound amplitude modulations or abrupt sound transients. These findings are consistent with the proposed involvement of the SPON in the processing of temporal sound structure, relevant for encoding communication cues. PMID:23515791

  20. Neuronal differentiation of hair-follicle-bulge-derived stem cells co-cultured with mouse cochlear modiolus explants.

    Directory of Open Access Journals (Sweden)

    Timo Schomann

    Full Text Available Stem-cell-based repair of auditory neurons may represent an attractive therapeutic option to restore sensorineural hearing loss. Hair-follicle-bulge-derived stem cells (HFBSCs are promising candidates for this type of therapy, because they (1 have migratory properties, enabling migration after transplantation, (2 can differentiate into sensory neurons and glial cells, and (3 can easily be harvested in relatively high numbers. However, HFBSCs have never been used for this purpose. We hypothesized that HFBSCs can be used for cell-based repair of the auditory nerve and we have examined their migration and incorporation into cochlear modiolus explants and their subsequent differentiation. Modiolus explants obtained from adult wild-type mice were cultured in the presence of EF1α-copGFP-transduced HFBSCs, constitutively expressing copepod green fluorescent protein (copGFP. Also, modiolus explants without hair cells were co-cultured with DCX-copGFP-transduced HFBSCs, which demonstrate copGFP upon doublecortin expression during neuronal differentiation. Velocity of HFBSC migration towards modiolus explants was calculated, and after two weeks, co-cultures were fixed and processed for immunohistochemical staining. EF1α-copGFP HFBSC migration velocity was fast: 80.5 ± 6.1 μm/h. After arrival in the explant, the cells formed a fascicular pattern and changed their phenotype into an ATOH1-positive neuronal cell type. DCX-copGFP HFBSCs became green-fluorescent after integration into the explants, confirming neuronal differentiation of the cells. These results show that HFBSC-derived neuronal progenitors are migratory and can integrate into cochlear modiolus explants, while adapting their phenotype depending on this micro-environment. Thus, HFBSCs show potential to be employed in cell-based therapies for auditory nerve repair.

  1. Conductive Hearing Loss Has Long-Lasting Structural and Molecular Effects on Presynaptic and Postsynaptic Structures of Auditory Nerve Synapses in the Cochlear Nucleus.

    Science.gov (United States)

    Clarkson, Cheryl; Antunes, Flora M; Rubio, Maria E

    2016-09-28

    Sound deprivation by conductive hearing loss increases hearing thresholds, but little is known about the response of the auditory brainstem during and after conductive hearing loss. Here, we show in young adult rats that 10 d of monaural conductive hearing loss (i.e., earplugging) leads to hearing deficits that persist after sound levels are restored. Hearing thresholds in response to clicks and frequencies higher than 8 kHz remain increased after a 10 d recovery period. Neural output from the cochlear nucleus measured at 10 dB above threshold is reduced and followed by an overcompensation at the level of the lateral lemniscus. We assessed whether structural and molecular substrates at auditory nerve (endbulb of Held) synapses in the cochlear nucleus could explain these long-lasting changes in hearing processing. During earplugging, vGluT1 expression in the presynaptic terminal decreased and synaptic vesicles were smaller. Together, there was an increase in postsynaptic density (PSD) thickness and an upregulation of GluA3 AMPA receptor subunits on bushy cells. After earplug removal and a 10 d recovery period, the density of synaptic vesicles increased, vesicles were also larger, and the PSD of endbulb synapses was larger and thicker. The upregulation of the GluA3 AMPAR subunit observed during earplugging was maintained after the recovery period. This suggests that GluA3 plays a role in plasticity in the cochlear nucleus. Our study demonstrates that sound deprivation has long-lasting alterations on structural and molecular presynaptic and postsynaptic components at the level of the first auditory nerve synapse in the auditory brainstem. Despite being the second most prevalent form of hearing loss, conductive hearing loss and its effects on central synapses have received relatively little attention. Here, we show that 10 d of monaural conductive hearing loss leads to an increase in hearing thresholds, to an increased central gain upstream of the cochlear nucleus at

  2. Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

    Science.gov (United States)

    Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

    2015-01-01

    Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

  3. Systemic Glucoregulation by Glucose-Sensing Neurons in the Ventromedial Hypothalamic Nucleus (VMH).

    Science.gov (United States)

    Shimazu, Takashi; Minokoshi, Yasuhiko

    2017-05-01

    The ventromedial hypothalamic nucleus (VMH) regulates glucose production in the liver as well as glucose uptake and utilization in peripheral tissues, including skeletal muscle and brown adipose tissue, via efferent sympathetic innervation and neuroendocrine mechanisms. The action of leptin on VMH neurons also increases glucose uptake in specific peripheral tissues through the sympathetic nervous system, with improved insulin sensitivity. On the other hand, subsets of VMH neurons, such as those that express steroidogenic factor 1 (SF1), sense changes in the ambient glucose concentration and are characterized as glucose-excited (GE) and glucose-inhibited (GI) neurons whose action potential frequency increases and decreases, respectively, as glucose levels rise. However, how these glucose-sensing (GE and GI) neurons in the VMH contribute to systemic glucoregulation remains poorly understood. In this review, we provide historical background and discuss recent advances related to glucoregulation by VMH neurons. In particular, the article describes the role of GE neurons in the control of peripheral glucose utilization and insulin sensitivity, which depend on mitochondrial uncoupling protein 2 of the neurons, as well as that of GI neurons in the control of hepatic glucose production through hypoglycemia-induced counterregulatory mechanisms.

  4. Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice.

    Science.gov (United States)

    Marshall, Christopher J; Desroziers, Elodie; McLennan, Timothy; Campbell, Rebecca E

    2017-01-01

    Arcuate nucleus (ARN) γ-aminobutyric acid (GABA) neurons are implicated in many critical homeostatic mechanisms, from food intake to fertility. To determine the functional relevance of ARN GABA neurons, it is essential to define the neurotransmitters co-expressed with and potentially co-released from ARN GABA neurons. The present study investigated the expression of markers of specific signaling molecules by ARN GABA neurons in brain sections from male, female, and, in some cases, prenatally androgen-treated (PNA) female, vesicular GABA transporter (VGaT)-ires-Cre/tdTomato reporter mice. Immunofluorescence for kisspeptin, β-endorphin, neuropeptide Y (NPY), tyrosine hydroxylase (TH) and neuronal nitric oxide synthase (nNOS) was detected by confocal microscopy, and co-localization with tdTomato VGaT reporter expression throughout the ARN was quantified. GABA neurons rarely co-localized with kisspeptin (95%) co-localized with VGaT across groups. Both TH and nNOS labeling was co-localized with ∼10% of ARN GABA neurons. The proportion of TH neurons co-localized with VGaT was significantly greater in males than either control or PNA females, and the proportion of nNOS neurons co-localizing VGaT was higher in control and PNA females compared with males. These data highlight NPY as a significant subpopulation of ARN GABA neurons, demonstrate no significant impact of PNA on signal co-expression, and, for the first time, show sexually dimorphic co-expression patterns of TH and nNOS with ARN GABA neurons. © 2016 S. Karger AG, Basel.

  5. Effects of cevimeline on excitability of parasympathetic preganglionic neurons in the superior salivatory nucleus of rats.

    Science.gov (United States)

    Mitoh, Yoshihiro; Ueda, Hirotaka; Ichikawa, Hiroyuki; Fujita, Masako; Kobashi, Motoi; Matsuo, Ryuji

    2017-09-01

    The superior salivatory nucleus (SSN) contains parasympathetic preganglionic neurons innervating the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, is a sialogogue that possibly stimulates SSN neurons in addition to the salivary glands themselves because it can cross the blood-brain barrier (BBB). In the present study, we examined immunoreactivities for mAChR subtypes in SSN neurons retrogradely labeled with a fluorescent tracer in neonatal rats. Additionally, we examined the effects of cevimeline in labeled SSN neurons of brainstem slices using a whole-cell patch-clamp technique. Mainly M1 and M3 receptors were detected by immunohistochemical staining, with low-level detection of M4 and M5 receptors and absence of M2 receptors. Most (110 of 129) SSN neurons exhibited excitatory responses to application of cevimeline. In responding neurons, voltage-clamp recordings showed that 84% (101/120) of the neurons exhibited inward currents. In the neurons displaying inward currents, the effects of the mAChR antagonists were examined. A mixture of M1 and M3 receptor antagonists most effectively reduced the peak amplitude of inward currents, suggesting that the excitatory effects of cevimeline on SSN neurons were mainly mediated by M1 and M3 receptors. Current-clamp recordings showed that application of cevimeline induced membrane depolarization (9/9 neurons). These results suggest that most SSN neurons are excited by cevimeline via M1 and M3 muscarinic receptors. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Nesfatin-1 activates cardiac vagal neurons of nucleus ambiguus and elicits bradycardia in conscious rats.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Tica, Andrei A; Rabinowitz, Joseph E; Tilley, Douglas G; Benamar, Khalid; Koch, Walter J; Brailoiu, Eugen

    2013-09-01

    Nesfatin-1, a peptide whose receptor is yet to be identified, has been involved in the modulation of feeding, stress, and metabolic responses. More recently, increasing evidence supports a modulatory role for nesfatin-1 in autonomic and cardiovascular activity. This study was undertaken to test if the expression of nesfatin-1 in the nucleus ambiguus, a key site for parasympathetic cardiac control, may be correlated with a functional role. As we have previously demonstrated that nesfatin-1 elicits Ca²⁺ signaling in hypothalamic neurons, we first assessed the effect of this peptide on cytosolic Ca²⁺ in cardiac pre-ganglionic neurons of nucleus ambiguus. We provide evidence that nesfatin-1 increases cytosolic Ca²⁺ concentration via a Gi/o-coupled mechanism. The nesfatin-1-induced Ca²⁺ rise is critically dependent on Ca²⁺ influx via P/Q-type voltage-activated Ca²⁺ channels. Repeated administration of nesfatin-1 leads to tachyphylaxis. Furthermore, nesfatin-1 produces a dose-dependent depolarization of cardiac vagal neurons via a Gi/o-coupled mechanism. In vivo studies, using telemetric and tail-cuff monitoring of heart rate and blood pressure, indicate that microinjection of nesfatin-1 into the nucleus ambiguus produces bradycardia not accompanied by a change in blood pressure in conscious rats. Taken together, our results identify for the first time that nesfatin-1 decreases heart rate by activating cardiac vagal neurons of nucleus ambiguus. Our results indicate that nesfatin-1, one of the most potent feeding peptides, increases cytosolic Ca²⁺ by promoting Ca²⁺ influx via P/Q channels and depolarizes nucleus ambiguus neurons; both effects are Gi/o-mediated. In vivo studies indicate that microinjection of nesfatin-1 into nucleus ambiguus produces bradycardia in conscious rats. This is the first report that nesfatin-1 increases the parasympathetic cardiac tone. © 2013 International Society for Neurochemistry.

  7. Hearing in action; auditory properties of neurones in the red nucleus of alert primates

    Directory of Open Access Journals (Sweden)

    Jonathan Murray Lovell

    2014-05-01

    Full Text Available The response of neurones in the Red Nucleus pars magnocellularis (RNm to both tone bursts and electrical stimulation were observed in three cynomolgus monkeys (Macaca fascicularis, in a series of studies primarily designed to characterise the influence of the dopaminergic ventral midbrain on auditory processing. Compared to its role in motor behaviour, little is known about the sensory response properties of neurons in the red nucleus; particularly those concerning the auditory modality. Sites in the RN were recognised by observing electrically evoked body movements characteristic for this deep brain structure. In this study we applied brief monopolar electrical stimulation to 118 deep brain sites at a maximum intensity of 200 µA, thus evoking minimal body movements. Auditory sensitivity of RN neurons was analysed more thoroughly at 15 sites, with the majority exhibiting broad tuning curves and phase locking up to 1.03 kHz. Since the RN appears to receive inputs from a very early stage of the ascending auditory system, our results suggest that sounds can modify the motor control exerted by this brain nucleus. At selected locations, we also tested for the presence of functional connections between the RN and the auditory cortex by inserting additional microelectrodes into the auditory cortex and investigating how action potentials and local field potentials were affected by electrical stimulation of the RN.

  8. Cochlear implants: 100 pediatric case conversions from the body worn to the nucleus esprit 22 ear level speech processor.

    Science.gov (United States)

    Dodd, M C; Nikolopoulos, T P; Totten, C; Cope, Y; O'Donoghue, G M

    2005-07-01

    To assess performance of Nucleus 22 mini system pediatric users converted from the Spectra 22 body-worn to the ESPrit 22 ear-level speech processor using aided thresholds and speech discrimination measures before and after the conversion. Spectra 22 body-worn speech processor users were chosen using preselection criteria (stable map, ability to report on the quality of the signal, no device problems). The subjects underwent tuning, map conversion, fitting of the ESPrit 22, and aided soundfield threshold and speech discrimination testing. The first 100 consecutive conversions are analyzed in this study. Fifty children (50%) were female, and 50 (50%) were male. The average age at implantation was 4.6 years (median 4.3 years, range 1.7 to 11 years). The average age of fitting the ear level speech processor was 11.1 years (median 11 years, range 6.2 to 18.2 years). Tertiary referral pediatric cochlear implant center in the United Kingdom. Of the 100 fittings attempted, all Spectra 22 maps could to be converted for use in the ESPrit 22. Of these 100 fittings, 44 were straightforward with no adjustment to map parameters being required, and 56 needed rate reductions and other map adjustments to achieve the conversion. The difference of the mean thresholds before and after the conversion did not exceed 2 dB across the frequencies studied (0.5-4 kHz). In 95% of the cases, the differences were less than 9 dB(A). With regard to speech discrimination testing, the mean threshold before the conversion was 53.4 dB and after the conversion 52.7 dB. Of the 100 conversions, only five children stopped using the ESPrit 22 despite fitting being achieved. Conversion from the Spectra 22 body worn to the ESPrit 22 ear level speech processor was found to be feasible in all the 100 cases studied. Only a minority (5%) of children chose not to use the ear level speech processor suggesting that children and parents were satisfied from the conversion.

  9. Glucose and insulin induce Ca2+ signaling in nesfatin-1 neurons in the hypothalamic paraventricular nucleus.

    Science.gov (United States)

    Gantulga, Darambazar; Maejima, Yuko; Nakata, Masanori; Yada, Toshihiko

    2012-04-20

    Nucleobindin-2 derived nesfatin-1 in the hypothalamic paraventricular nucleus (PVN) plays a role in inhibition of feeding. The neural pathways downstream of PVN nesfatin-1 have been extensively investigated. However, regulation of the PVN nesfatin-1 neurons remains unclear. Since starvation decreases and refeeding stimulates nesfatin-1 expression specifically in the PVN, this study aimed to clarify direct effects of meal-evoked metabolic factors, glucose and insulin, on PVN nesfatin-1 neurons. High glucose (10mM) and insulin (10(-13)M) increased cytosolic calcium concentration ([Ca(2+)](i)) in 55 of 331 (16.6%) and 32 of 249 (12.9%) PVN neurons, respectively. Post [Ca(2+)](i) measurement immunocytochemistry identified that 58.2% of glucose-responsive and 62.5% of insulin-responsive neurons were immunoreactive to nesfatin-1. Furthermore, a fraction of the glucose-responsive nesfatin-1 neurons also responded to insulin, and vice versa. Some of the neurons that responded to neither glucose nor insulin were recruited to [Ca(2+)](i) increases by glucose and insulin in combination. Our data demonstrate that glucose and insulin directly interact with and increase [Ca(2+)](i) in nesfatin-1 neurons in the PVN, and that the nesfatin-1 neuron is the primary target for them in the PVN. The results suggest that high glucose- and insulin-induced activation of PVN nesfatin-1 neurons serves as a mechanism through which meal ingestion stimulates nesfatin-1 neurons in the PVN and thereby produces satiety. Copyright © 2012 Elsevier Inc. All rights reserved.

  10. Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability.

    Science.gov (United States)

    Fujita, Akie; Bonnavion, Patricia; Wilson, Miryam H; Mickelsen, Laura E; Bloit, Julien; de Lecea, Luis; Jackson, Alexander C

    2017-09-27

    Histaminergic (HA) neurons, found in the posterior hypothalamic tuberomammillary nucleus (TMN), extend fibers throughout the brain and exert modulatory influence over numerous physiological systems. Multiple lines of evidence suggest that the activity of HA neurons is important in the regulation of vigilance despite the lack of direct, causal evidence demonstrating its requirement for the maintenance of arousal during wakefulness. Given the strong correlation between HA neuron excitability and behavioral arousal, we investigated both the electrophysiological diversity of HA neurons in brain slices and the effect of their acute silencing in vivo in male mice. For this purpose, we first validated a transgenic mouse line expressing cre recombinase in histidine decarboxylase-expressing neurons ( Hdc -Cre) followed by a systematic census of the membrane properties of both HA and non-HA neurons in the ventral TMN (TMNv) region. Through unsupervised hierarchical cluster analysis, we found electrophysiological diversity both between TMNv HA and non-HA neurons, and among HA neurons. To directly determine the impact of acute cessation of HA neuron activity on sleep-wake states in awake and behaving mice, we examined the effects of optogenetic silencing of TMNv HA neurons in vivo We found that acute silencing of HA neurons during wakefulness promotes slow-wave sleep, but not rapid eye movement sleep, during a period of low sleep pressure. Together, these data suggest that the tonic firing of HA neurons is necessary for the maintenance of wakefulness, and their silencing not only impairs arousal but is sufficient to rapidly and selectively induce slow-wave sleep. SIGNIFICANCE STATEMENT The function of monoaminergic systems and circuits that regulate sleep and wakefulness is often disrupted as part of the pathophysiology of many neuropsychiatric disorders. One such circuit is the posterior hypothalamic histamine (HA) system, implicated in supporting wakefulness and higher brain

  11. Dexmedetomidine decreases inhibitory but not excitatory neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Sharp, Douglas B; Wang, Xin; Mendelowitz, David

    2014-07-29

    Dexmedetomidine, an α2 adrenergic agonist, is a useful sedative but can also cause significant bradycardia. This decrease in heart rate may be due to decreased central sympathetic output as well as increased parasympathetic output from brainstem cardiac vagal neurons. In this study, using whole cell voltage clamp methodology, the actions of dexmedetomidine on excitatory glutamatergic and inhibitory GABAergic and glycinergic neurotransmission to parasympathetic cardiac vagal neurons in the rat nucleus ambiguus was determined. The results indicate that dexmedetomidine decreases both GABAergic and glycinergic inhibitory input to cardiac vagal neurons, with no significant effect on excitatory input. These results provide a mechanism for dexmedetomidine induced bradycardia and has implications for the management of this potentially harmful side effect. Copyright © 2014 Elsevier B.V. All rights reserved.

  12. Reduced Slc6a15 in Nucleus Accumbens D2-Neurons Underlies Stress Susceptibility.

    Science.gov (United States)

    Chandra, Ramesh; Francis, T Chase; Nam, Hyungwoo; Riggs, Lace M; Engeln, Michel; Rudzinskas, Sarah; Konkalmatt, Prasad; Russo, Scott J; Turecki, Gustavo; Iniguez, Sergio D; Lobo, Mary Kay

    2017-07-05

    Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility. SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

  13. TASK-2 Channels Contribute to pH Sensitivity of Retrotrapezoid Nucleus Chemoreceptor Neurons

    Science.gov (United States)

    Wang, Sheng; Benamer, Najate; Zanella, Sébastien; Kumar, Natasha N.; Shi, Yingtang; Bévengut, Michelle; Penton, David; Guyenet, Patrice G.; Lesage, Florian

    2013-01-01

    Phox2b-expressing glutamatergic neurons of the retrotrapezoid nucleus (RTN) display properties expected of central respiratory chemoreceptors; they are directly activated by CO2/H+ via an unidentified pH-sensitive background K+ channel and, in turn, facilitate brainstem networks that control breathing. Here, we used a knock-out mouse model to examine whether TASK-2 (K2P5), an alkaline-activated background K+ channel, contributes to RTN neuronal pH sensitivity. We made patch-clamp recordings in brainstem slices from RTN neurons that were identified by expression of GFP (directed by the Phox2b promoter) or β-galactosidase (from the gene trap used for TASK-2 knock-out). Whereas nearly all RTN cells from control mice were pH sensitive (95%, n = 58 of 61), only 56% of GFP-expressing RTN neurons from TASK-2−/− mice (n = 49 of 88) could be classified as pH sensitive (>30% reduction in firing rate from pH 7.0 to pH 7.8); the remaining cells were pH insensitive (44%). Moreover, none of the recorded RTN neurons from TASK-2−/− mice selected based on β-galactosidase activity (a subpopulation of GFP-expressing neurons) were pH sensitive. The alkaline-activated background K+ currents were reduced in amplitude in RTN neurons from TASK-2−/− mice that retained some pH sensitivity but were absent from pH-insensitive cells. Finally, using a working heart–brainstem preparation, we found diminished inhibition of phrenic burst amplitude by alkalization in TASK-2−/− mice, with apneic threshold shifted to higher pH levels. In conclusion, alkaline-activated TASK-2 channels contribute to pH sensitivity in RTN neurons, with effects on respiration in situ that are particularly prominent near apneic threshold. PMID:24107938

  14. Temperature manipulation of neuronal dynamics in a forebrain motor control nucleus.

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    Matías A Goldin

    2017-08-01

    Full Text Available Different neuronal types within brain motor areas contribute to the generation of complex motor behaviors. A widely studied songbird forebrain nucleus (HVC has been recognized as fundamental in shaping the precise timing characteristics of birdsong. This is based, among other evidence, on the stretching and the "breaking" of song structure when HVC is cooled. However, little is known about the temperature effects that take place in its neurons. To address this, we investigated the dynamics of HVC both experimentally and computationally. We developed a technique where simultaneous electrophysiological recordings were performed during temperature manipulation of HVC. We recorded spontaneous activity and found three effects: widening of the spike shape, decrease of the firing rate and change in the interspike interval distribution. All these effects could be explained with a detailed conductance based model of all the neurons present in HVC. Temperature dependence of the ionic channel time constants explained the first effect, while the second was based in the changes of the maximal conductance using single synaptic excitatory inputs. The last phenomenon, only emerged after introducing a more realistic synaptic input to the inhibitory interneurons. Two timescales were present in the interspike distributions. The behavior of one timescale was reproduced with different input balances received form the excitatory neurons, whereas the other, which disappears with cooling, could not be found assuming poissonian synaptic inputs. Furthermore, the computational model shows that the bursting of the excitatory neurons arises naturally at normal brain temperature and that they have an intrinsic delay at low temperatures. The same effect occurs at single synapses, which may explain song stretching. These findings shed light on the temperature dependence of neuronal dynamics and present a comprehensive framework to study neuronal connectivity. This study, which

  15. Dietary grape seed polyphenols repress neuron and glia activation in trigeminal ganglion and trigeminal nucleus caudalis

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    Durham Paul L

    2010-12-01

    Full Text Available Abstract Background Inflammation and pain associated with temporomandibular joint disorder, a chronic disease that affects 15% of the adult population, involves activation of trigeminal ganglion nerves and development of peripheral and central sensitization. Natural products represent an underutilized resource in the pursuit of safe and effective ways to treat chronic inflammatory diseases. The goal of this study was to investigate effects of grape seed extract on neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis in response to persistent temporomandibular joint inflammation. Sprague Dawley rats were pretreated with 200 mg/kg/d MegaNatural-BP grape seed extract for 14 days prior to bilateral injections of complete Freund's adjuvant into the temporomandibular joint capsule. Results In response to grape seed extract, basal expression of mitogen-activated protein kinase phosphatase 1 was elevated in neurons and glia in trigeminal ganglia and trigeminal nucleus caudalis, and expression of the glutamate aspartate transporter was increased in spinal glia. Rats on a normal diet injected with adjuvant exhibited greater basal levels of phosphorylated-p38 in trigeminal ganglia neurons and spinal neurons and microglia. Similarly, immunoreactive levels of OX-42 in microglia and glial fibrillary acidic protein in astrocytes were greatly increased in response to adjuvant. However, adjuvant-stimulated levels of phosphorylated-p38, OX-42, and glial fibrillary acidic protein were significantly repressed in extract treated animals. Furthermore, grape seed extract suppressed basal expression of the neuropeptide calcitonin gene-related peptide in spinal neurons. Conclusions Results from our study provide evidence that grape seed extract may be beneficial as a natural therapeutic option for temporomandibular joint disorders by suppressing development of peripheral and central sensitization.

  16. Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat.

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    Bertrand Degos

    Full Text Available Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

  17. Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus?

    Science.gov (United States)

    Matamales, Miriam

    2012-12-19

    Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

  18. Responses of Rostral Fastigial Nucleus Neurons of Conscious Cats to Rotations in Vertical Planes

    Science.gov (United States)

    Miller, D. M.; Cotter, L.A.; Gandhi, N. J.; Schor, R. H.; Huff, N. O.; Raj, S. G.; Shulman, J. A.; Yates, B. J.

    2008-01-01

    The rostral fastigial nucleus (RFN) of the cerebellum is thought to play an important role in postural control, and recent studies in conscious nonhuman primates suggest that this region also participates in the sensory processing required to compute body motion in space. The goal of the present study was to examine the dynamic and spatial responses to sinusoidal rotations in vertical planes of RFN neurons in conscious cats, and determine if they are similar to responses reported for monkeys. Approximately half of the RFN neurons examined were classified as graviceptive, since their firing was synchronized with stimulus position and the gain of their responses was relatively unaffected by the frequency of the tilts. The large majority (80%) of graviceptive RFN neurons were activated by pitch rotations. Most of the remaining RFN units exhibited responses to vertical oscillations that encoded stimulus velocity, and approximately 50% of these velocity units had a response vector orientation aligned near the plane of a single vertical semicircular canal. Unlike in primates, few feline RFN neurons had responses to vertical rotations that suggested integration of graviceptive (otolith) and velocity (vertical semicircular canal) signals. These data indicate that the physiological role of the RFN may differ between primates and lower mammals. The RFN in rats and cats in known to be involved in adjusting blood pressure and breathing during postural alterations in the transverse (pitch) plane. The relatively simple responses of many RFN neurons in cats are appropriate for triggering such compensatory autonomic responses. PMID:18571332

  19. Age-related changes in functional postsynaptic nAChR subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction

    DEFF Research Database (Denmark)

    Christensen, Mark Holm; Kohlmeier, Kristi Anne

    2016-01-01

    the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons...

  20. Identifying cochlear implant channels with poor electrode-neuron interface: partial tripolar, single-channel thresholds and psychophysical tuning curves.

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F

    2010-04-01

    The goal of this study was to evaluate the ability of a threshold measure, made with a restricted electrode configuration, to identify channels exhibiting relatively poor spatial selectivity. With a restricted electrode configuration, channel-to-channel variability in threshold may reflect variations in the interface between the electrodes and auditory neurons (i.e., nerve survival, electrode placement, and tissue impedance). These variations in the electrode-neuron interface should also be reflected in psychophysical tuning curve (PTC) measurements. Specifically, it is hypothesized that high single-channel thresholds obtained with the spatially focused partial tripolar (pTP) electrode configuration are predictive of wide or tip-shifted PTCs. Data were collected from five cochlear implant listeners implanted with the HiRes90k cochlear implant (Advanced Bionics Corp., Sylmar, CA). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the pTP configuration for which a fraction of current (sigma) from a center-active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. Forward-masked PTCs were obtained for channels with the highest, lowest, and median tripolar (sigma = 1 or 0.9) thresholds. The probe channel and level were fixed and presented with either the monopolar (sigma = 0) or a more focused pTP (sigma > or = 0.55) configuration. The masker channel and level were varied, whereas the configuration was fixed to sigma = 0.5. A standard, three-interval, two-alternative forced choice procedure was used for thresholds and masked levels. Single-channel threshold and variability in threshold across channels systematically increased as the compensating current, sigma, increased and the presumed electrical field became more focused. Across subjects, channels with the highest single-channel thresholds, when measured with a

  1. Two distinct populations of projection neurons in the rat lateral parafascicular thalamic nucleus and their cholinergic responsiveness.

    Science.gov (United States)

    Beatty, J A; Sylwestrak, E L; Cox, C L

    2009-08-04

    The lateral parafascicular nucleus (lPf) is a member of the intralaminar thalamic nuclei, a collection of nuclei that characteristically provides widespread projections to the neocortex and basal ganglia and is associated with arousal, sensory, and motor functions. Recently, lPf neurons have been shown to possess different characteristics than other cortical-projecting thalamic relay neurons. We performed whole cell recordings from lPf neurons using an in vitro rat slice preparation and found two distinct neuronal subtypes that were differentiated by distinct morphological and physiological characteristics: diffuse and bushy. Diffuse neurons, which had been previously described, were the predominant neuronal subtype (66%). These neurons had few, poorly-branching, extended dendrites, and rarely displayed burst-like action potential discharge, a ubiquitous feature of thalamocortical relay neurons. Interestingly, we discovered a smaller population of bushy neurons (34%) that shared similar morphological and physiological characteristics with thalamocortical relay neurons of primary sensory thalamic nuclei. In contrast to other thalamocortical relay neurons, activation of muscarinic cholinergic receptors produced a membrane hyperpolarization via activation of M(2) receptors in most lPf neurons (60%). In a minority of lPf neurons (33%), muscarinic agonists produced a membrane depolarization via activation of predominantly M(3) receptors. The muscarinic receptor-mediated actions were independent of lPf neuronal subtype (i.e. diffuse or bushy neurons); however the cholinergic actions were correlated with lPf neurons with different efferent targets. Retrogradely-labeled lPf neurons from frontal cortical fluorescent bead injections primarily consisted of bushy type lPf neurons (78%), but more importantly, all of these neurons were depolarized by muscarinic agonists. On the other hand, lPf neurons labeled by striatal injections were predominantly hyperpolarized by muscarinic

  2. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus

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    Li Zhou

    2017-03-01

    Full Text Available Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN.

  3. Rhythmic Firing of Pedunculopontine Tegmental Nucleus Neurons in Monkeys during Eye Movement Task.

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    Ken-Ichi Okada

    Full Text Available The pedunculopontine tegmental nucleus (PPTN has been thought to be involved in the control of behavioral state. Projections to the entire thalamus and reciprocal connections with the basal ganglia nuclei suggest a potential role for the PPTN in the control of various rhythmic behaviors, including waking/sleeping and locomotion. Recently, rhythmic activity in the local field potentials was recorded from the PPTN of patients with Parkinson's disease who were treated with levodopa, suggesting that rhythmic firing is a feature of the functioning PPTN and might change with the behaving conditions even within waking. However, it remains unclear whether and how single PPTN neurons exhibit rhythmic firing patterns during various behaving conditions, including executing conditioned eye movement behaviors, seeking reward, or during resting. We previously recorded from PPTN neurons in healthy monkeys during visually guided saccade tasks and reported task-related changes in firing rate, and in this paper, we reanalyzed these data and focused on their firing patterns. A population of PPTN neurons demonstrated a regular firing pattern in that the coefficient of variation of interspike intervals was lower than what would be expected of theoretical random and irregular spike trains. Furthermore, a group of PPTN neurons exhibited a clear periodic single spike firing that changed with the context of the behavioral task. Many of these neurons exhibited a periodic firing pattern during highly active conditions, either the fixation condition during the saccade task or the free-viewing condition during the intertrial interval. We speculate that these task context-related changes in rhythmic firing of PPTN neurons might regulate the monkey's attentional and vigilance state to perform the task.

  4. Distinctive features of Phox2b-expressing neurons in the rat reticular formation dorsal to the trigeminal motor nucleus.

    Science.gov (United States)

    Nagoya, Kouta; Nakamura, Shiro; Ikeda, Keiko; Onimaru, Hiroshi; Yoshida, Atsushi; Nakayama, Kiyomi; Mochizuki, Ayako; Kiyomoto, Masaaki; Sato, Fumihiko; Kawakami, Kiyoshi; Takahashi, Koji; Inoue, Tomio

    2017-09-01

    Phox2b encodes a paired-like homeodomain-containing transcription factor essential for development of the autonomic nervous system. Phox2b-expressing (Phox2b + ) neurons are present in the reticular formation dorsal to the trigeminal motor nucleus (RdV) as well as the nucleus of the solitary tract and parafacial respiratory group. However, the nature of Phox2b + RdV neurons is still unclear. We investigated the physiological and morphological properties of Phox2b + RdV neurons using postnatal day 2-7 transgenic rats expressing yellow fluorescent protein under the control of Phox2b. Almost all of Phox2b + RdV neurons were glutamatergic, whereas Phox2b-negative (Phox2b - ) RdV neurons consisted of a few glutamatergic, many GABAergic, and many glycinergic neurons. The majority (48/56) of Phox2b + neurons showed low-frequency firing (LF), while most of Phox2b - neurons (35/42) exhibited high-frequency firing (HF) in response to intracellularly injected currents. All, but one, Phox2b + neurons (55/56) did not fire spontaneously, whereas three-fourths of the Phox2b - neurons (31/42) were spontaneously active. K + channel and persistent Na + current blockers affected the firing of LF and HF neurons. The majority of Phox2b + (35/46) and half of the Phox2b - neurons (19/40) did not respond to stimulations of the mesencephalic trigeminal nucleus, the trigeminal tract, and the principal sensory trigeminal nucleus. Biocytin labeling revealed that about half of the Phox2b + (5/12) and Phox2b - RdV neurons (5/10) send their axons to the trigeminal motor nucleus. These results suggest that Phox2b + RdV neurons have distinct neurotransmitter phenotypes and firing properties from Phox2b - RdV neurons and might play important roles in feeding-related functions including suckling and possibly mastication. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Estradiol target neurons in the hypothalamic arcuate nucleus and lateral ventromedial nucleus of young adult, reproductively senescent, and monosodium glutamate-lesioned female golden hamsters

    International Nuclear Information System (INIS)

    Blaha, G.C.; Lamperti, A.A.

    1983-01-01

    Histoautoradiographic methods were used to assess estrogen target neurons in the hypothalamic arcuate nucleus (ARC) and ventromedial nucleus, lateral portion (LVM), comparing young adult and aged female golden hamsters. A subgroup of young adult females had ARC lesions induced by monosodium glutamate at neonatal day 8. All were ovariectomized to remove endogenous estrogens. Controls were given nonradioactive estradiol. After 3 H-estradiol ( 3 H-E2) was injected intravenously, hypothalami were removed, frozen, and processed for histoautoradiography. In the ARC and LVM the ratio of 3 H-E2 labelled neurons to total neurons counted was significantly lower in the older animals. Young females with ARC lesions had very few 3 H-E2 labelled neurons remaining in the ARC but had a normal complement in the LVM. Although 3 H-E2 labelled ARC neurons were notably decreased in old females, those ARC neurons that were labelled in the old had virtually the same frequency distribution of the labelling index as in the young, suggesting no change in the average estrogen uptake per target cell

  6. Descending projections from the nucleus accumbens shell excite activity of taste-responsive neurons in the nucleus of the solitary tract in the hamster.

    Science.gov (United States)

    Li, Cheng-Shu; Lu, Da-Peng; Cho, Young K

    2015-06-01

    The nucleus of the solitary tract (NST) and the parabrachial nuclei (PbN) are the first and second relays in the rodent central taste pathway. A series of electrophysiological experiments revealed that spontaneous and taste-evoked activities of brain stem gustatory neurons are altered by descending input from multiple forebrain nuclei in the central taste pathway. The nucleus accumbens shell (NAcSh) is a key neural substrate of reward circuitry, but it has not been verified as a classical gustatory nucleus. A recent in vivo electrophysiological study demonstrated that the NAcSh modulates the spontaneous and gustatory activities of hamster pontine taste neurons. In the present study, we investigated whether activation of the NAcSh modulates gustatory responses of the NST neurons. Extracellular single-unit activity was recorded from medullary neurons in urethane-anesthetized hamsters. After taste response was confirmed by delivery of sucrose, NaCl, citric acid, and quinine hydrochloride to the anterior tongue, the NAcSh was stimulated bilaterally with concentric bipolar stimulating electrodes. Stimulation of the ipsilateral and contralateral NAcSh induced firings from 54 and 37 of 90 medullary taste neurons, respectively. Thirty cells were affected bilaterally. No inhibitory responses or antidromic invasion was observed after NAcSh activation. In the subset of taste cells tested, high-frequency electrical stimulation of the NAcSh during taste delivery enhanced taste-evoked neuronal firing. These results demonstrate that two-thirds of the medullary gustatory neurons are under excitatory descending influence from the NAcSh, which is a strong indication of communication between the gustatory pathway and the mesolimbic reward pathway. Copyright © 2015 the American Physiological Society.

  7. Encoding of naturalistic optic flow by motion sensitive neurons of nucleus rotundus in the zebra finch (Taeniopygia guttata.

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    Dennis eEckmeier

    2013-09-01

    Full Text Available The retinal image changes that occur during locomotion, the optic flow, carry information about self-motion and the three-dimensional structure of the environment. Especially fast moving animals with only little binocular vision depend on these depth cues for manoeuvring. They actively control their gaze to facilitate perception of depth based on cues in the optic flow. In the visual system of birds, nucleus rotundus neurons were originally found to respond to object motion but not to background motion. However, when background and object were both moving, responses increase the more the direction and velocity of object and background motion on the retina differed. These properties may play a role in representing depth cues in the optic flow. We therefore investigated how neurons in nucleus rotundus respond to optic flow that contains depth cues. We presented simplified and naturalistic optic flow on a panoramic LED display while recording from single neurons in nucleus rotundus of anaesthetized zebra finches. Unlike most studies on motion vision in birds, our stimuli included depth information.We found extensive responses of motion selective neurons in nucleus rotundus to optic flow stimuli. Simplified stimuli revealed preferences for optic flow reflecting translational or rotational self-motion. Naturalistic optic flow stimuli elicited complex response modulations, but the presence of objects was signalled by only few neurons. The neurons that did respond to objects in the optic flow, however, show interesting properties.

  8. CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis

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    Jackie Lau

    2018-01-01

    Full Text Available Objective: The cocaine- and amphetamine-regulated transcript (CART codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. Methods: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc and lateral hypothalamic area (LHA, respectively, was achieved. The effects on energy homeostasis control were investigated. Results: Here we show that CART neuron-specific reintroduction of CART into the Arc and LHA leads to distinct effects on energy homeostasis control. Specifically, CART reintroduction into the Arc of otherwise CART-deficient Cartcre/cre mice markedly decreased fat mass and body weight, whereas CART reintroduction into the LHA caused significant fat mass gain and lean mass loss, but overall unaltered body weight. The reduced adiposity in ArcCART;Cartcre/cre mice was associated with an increase in both energy expenditure and physical activity, along with significantly decreased Npy mRNA levels in the Arc but with no change in food consumption. Distinctively, the elevated fat mass in LHACART;Cartcre/cre mice was accompanied by diminished insulin responsiveness and glucose tolerance, greater spontaneous food intake, and reduced energy expenditure, which is consistent with the observed decrease of brown adipose tissue temperature. This is also in line with significantly reduced tyrosine hydroxylase (Th and notably increased corticotropin-releasing hormone (Crh mRNA expressions in the paraventricular nucleus (PVN. Conclusions: Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for

  9. Growth and atrophy of neurons labeled at their birth in a song nucleus of the zebra finch

    International Nuclear Information System (INIS)

    Konishi, M.; Akutagawa, E.

    1990-01-01

    The robust nucleus of the archistriatum (RA) is one of the forebrain nuclei that control song production in birds. In the zebra finch (Poephila guttata), this nucleus contains more and larger neurons in the male than in the female. A single injection of tritiated thymidine into the egg on the 6th or 7th day of incubation resulted in labeling of many RA neurons with tritium. The size of tritium-labeled neurons and the tissue volume containing them did not differ between the sexes at 15 days after hatching. In the adult brain, tritium-labeled neurons and the tissue volume containing them were much larger in the male than in the female. Also, tritium-labeled RA neurons were large in females which received an implant of estrogen immediately after hatching. The gender differences in the neuron size and nuclear volume of the zebra finch RA are, therefore, due not to the replacement of old neurons by new ones during development but to the growth and atrophy of neurons born before hatching. Similarly, the masculinizing effects of estrogen on the female RA are due not to neuronal replacement but to the prevention of atrophy and promotion of growth in preexisting neurons

  10. Divergent projections of catecholaminergic neurons in the nucleus of the solitary tract to limbic forebrain and medullary autonomic brain regions.

    Science.gov (United States)

    Reyes, Beverly A S; Van Bockstaele, Elisabeth J

    2006-10-30

    The nucleus of the solitary tract (NTS) is a critical structure involved in coordinating autonomic and visceral activities. Previous independent studies have demonstrated efferent projections from the NTS to the nucleus paragigantocellularis (PGi) and the central nucleus of the amygdala (CNA) in rat brain. To further characterize the neural circuitry originating from the NTS with postsynaptic targets in the amygdala and medullary autonomic targets, distinct green or red fluorescent latex microspheres were injected into the PGi and the CNA, respectively, of the same rat. Thirty-micron thick tissue sections through the lower brainstem and forebrain were collected. Every fourth section through the NTS region was processed for immunocytochemical detection of tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. Retrogradely labeled neurons from the PGi or CNA were distributed throughout the rostro-caudal segments of the NTS. However, the majority of neurons containing both retrograde tracers were distributed within the caudal third of the NTS. Cell counts revealed that approximately 27% of neurons projecting to the CNA in the NTS sent collateralized projections to the PGi while approximately 16% of neurons projecting to the PGi sent collateralized projections to the CNA. Interestingly, more than half of the PGi and CNA-projecting neurons in the NTS expressed TH immunoreactivity. These data indicate that catecholaminergic neurons in the NTS are poised to simultaneously coordinate activities in limbic and medullary autonomic brain regions.

  11. VGLUT1 or VGLUT2 mRNA-positive neurons in spinal trigeminal nucleus provide collateral projections to both the thalamus and the parabrachial nucleus in rats.

    Science.gov (United States)

    Zhang, Chun-Kui; Li, Zhi-Hong; Qiao, Yu; Zhang, Ting; Lu, Ya-Cheng; Chen, Tao; Dong, Yu-Lin; Li, Yun-Qing; Li, Jin-Lian

    2018-04-12

    The trigemino-thalamic (T-T) and trigemino-parabrachial (T-P) pathways are strongly implicated in the sensory-discriminative and affective/emotional aspects of orofacial pain, respectively. These T-T and T-P projection fibers originate from the spinal trigeminal nucleus (Vsp). We previously determined that many vesicular glutamate transporter (VGLUT1 and/or VGLUT2) mRNA-positive neurons were distributed in the Vsp of the adult rat, and most of these neurons sent their axons to the thalamus or cerebellum. However, whether VGLUT1 or VGLUT2 mRNA-positive projection neurons exist that send their axons to both the thalamus and the parabrachial nucleus (PBN) has not been reported. Thus, in the present study, dual retrograde tract tracing was used in combination with fluorescence in situ hybridization (FISH) for VGLUT1 or VGLUT2 mRNA to identify the existence of VGLUT1 or VGLUT2 mRNA neurons that send collateral projections to both the thalamus and the PBN. Neurons in the Vsp that send collateral projections to both the thalamus and the PBN were mainly VGLUT2 mRNA-positive, with a proportion of 90.3%, 93.0% and 85.4% in the oral (Vo), interpolar (Vi) and caudal (Vc) subnucleus of the Vsp, respectively. Moreover, approximately 34.0% of the collateral projection neurons in the Vc showed Fos immunopositivity after injection of formalin into the lip, and parts of calcitonin gene-related peptide (CGRP)-immunopositive axonal varicosities were in direct contact with the Vc collateral projection neurons. These results indicate that most collateral projection neurons in the Vsp, particularly in the Vc, which express mainly VGLUT2, may relay orofacial nociceptive information directly to the thalamus and PBN via axon collaterals.

  12. Nucleus accumbens neuronal maturation differences in young rats bred for low versus high voluntary running behaviour

    Science.gov (United States)

    Roberts, Michael D; Toedebusch, Ryan G; Wells, Kevin D; Company, Joseph M; Brown, Jacob D; Cruthirds, Clayton L; Heese, Alexander J; Zhu, Conan; Rottinghaus, George E; Childs, Thomas E; Booth, Frank W

    2014-01-01

    We compared the nucleus accumbens (NAc) transcriptomes of generation 8 (G8), 34-day-old rats selectively bred for low (LVR) versus high voluntary running (HVR) behaviours in rats that never ran (LVRnon-run and HVRnon-run), as well as in rats after 6 days of voluntary wheel running (LVRrun and HVRrun). In addition, the NAc transcriptome of wild-type Wistar rats was compared. The purpose of this transcriptomics approach was to generate testable hypotheses as to possible NAc features that may be contributing to running motivation differences between lines. Ingenuity Pathway Analysis and Gene Ontology analyses suggested that ‘cell cycle’-related transcripts and the running-induced plasticity of dopamine-related transcripts were lower in LVR versus HVR rats. From these data, a hypothesis was generated that LVR rats might have less NAc neuron maturation than HVR rats. Follow-up immunohistochemistry in G9–10 LVRnon-run rats suggested that the LVR line inherently possessed fewer mature medium spiny (Darpp-32-positive) neurons (P running wheel access in our G9–10 LVRs uniquely increased their Darpp-32-positive and Dcx-positive neuron densities. In summary, NAc cellularity differences and/or the lack of running-induced plasticity in dopamine signalling-related transcripts may contribute to low voluntary running motivation in LVR rats. PMID:24665095

  13. Orexins excite ventrolateral geniculate nucleus neurons predominantly via OX2 receptors.

    Science.gov (United States)

    Chrobok, Lukasz; Palus, Katarzyna; Lewandowski, Marian Henryk

    2016-04-01

    Orexins/hypocretins are two neuropeptides that influence many behaviours, such as feeding, sleep or arousal. Orexin A/hypocretin-1 (OXA) and orexin B/hypocretin-2 (OXB) bind to two metabotropic receptors, named the OX1 and OX2 receptors. The lateral geniculate complex of the thalamus is one of the many targets of orexinergic fibres derived from the lateral hypothalamus, although the impact of orexins on the ventrolateral geniculate nucleus (VLG) is poorly understood. The VLG, an important relay station of the subcortical visual system, is implicated in visuomotor and/or circadian processes. Therefore, in this study we evaluated the effects of orexins on single VLG neurons using a patch-clamp technique in vitro. Surprisingly, orexins depolarised the majority of the recorded neurons regardless of their localisation in the borders of the VLG. In addition, data presented in this article show that neurons synthesising NO were also affected by OXA. Moreover, immunohistochemical staining of OXB revealed the moderate density of orexinergic fibbers in the VLG. Our study using specific orexin receptor antagonists suggests that the OX2 receptor has a dominant role in the observed effects of OXA. To our knowledge, this article is the first to show orexinergic modulation of the VLG. These findings strengthen the postulated link between orexins and the circadian system, and propose a new role of these neuropeptides in the modulation of visuomotor functions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. The projection and synaptic organisation of NTS afferent connections with presympathetic neurons, GABA and nNOS neurons in the paraventricular nucleus of the hypothalamus

    Science.gov (United States)

    Affleck, V.S.; Coote, J.H.; Pyner, S.

    2012-01-01

    Elevated sympathetic nerve activity, strongly associated with cardiovascular disease, is partly generated from the presympathetic neurons of the paraventricular nucleus of the hypothalamus (PVN). The PVN-presympathetic neurons regulating cardiac and vasomotor sympathetic activity receive information about cardiovascular status from receptors in the heart and circulation. These receptors signal changes via afferent neurons terminating in the nucleus tractus solitarius (NTS), some of which may result in excitation or inhibition of PVN-presympathetic neurons. Understanding the anatomy and neurochemistry of NTS afferent connections within the PVN could provide important clues to the impairment in homeostasis cardiovascular control associated with disease. Transynaptic labelling has shown the presence of neuronal nitric oxide synthase (nNOS)-containing neurons and GABA interneurons that terminate on presympathetic PVN neurons any of which may be the target for NTS afferents. So far NTS connections to these diverse neuronal pools have not been demonstrated and were investigated in this study. Anterograde (biotin dextran amine – BDA) labelling of the ascending projection from the NTS and retrograde (fluorogold – FG or cholera toxin B subunit – CTB) labelling of PVN presympathetic neurons combined with immunohistochemistry for GABA and nNOS was used to identify the terminal neuronal targets of the ascending projection from the NTS. It was shown that NTS afferent terminals are apposed to either PVN-GABA interneurons or to nitric oxide producing neurons or even directly to presympathetic neurons. Furthermore, there was evidence that some NTS axons were positive for vesicular glutamate transporter 2 (vGLUT2). The data provide an anatomical basis for the different functions of cardiovascular receptors that mediate their actions via the NTS–PVN pathways. PMID:22698695

  15. H2O2 INDUCES DELAYED HYPEREXCITABILITY IN NUCLEUS TRACTUS SOLITARII NEURONS

    Science.gov (United States)

    Ostrowski, Tim D.; Hasser, Eileen M.; Heesch, Cheryl M.; Kline, David D.

    2014-01-01

    Hydrogen peroxide (H2O2) is a stable reactive oxygen species and potent neuromodulator of cellular and synaptic activity. Centrally, endogenous H2O2 is elevated during bouts of hypoxia-reoxygenation, a variety of disease states, and aging. The nucleus tractus solitarii (nTS) is the central termination site of visceral afferents for homeostatic reflexes and contributes to reflex alterations during these conditions. We determined the extent to which H2O2 modulates synaptic and membrane properties in nTS neurons in rat brainstem slices. Stimulation of the tractus solitarii (which contains the sensory afferent fibers) evoked synaptic currents that were not altered by 10 – 500 μM H2O2. However, 500 μM H2O2 modulated several intrinsic membrane properties of nTS neurons, including a decrease in input resistance, hyperpolarization of resting membrane potential (RMP) and action potential (AP) threshold (THR), and an initial reduction in AP discharge to depolarizing current. H2O2 increased conductance of barium-sensitive potassium currents, and block of these currents ablated H2O2-induced changes in RMP, input resistance and AP discharge. Following washout of H2O2 AP discharge was enhanced due to depolarization of RMP and a partially maintained hyperpolarization of THR. Hyperexcitability persisted with repeated H2O2 exposure. H2O2 effects on RMP and THR were ablated by intracellular administration of the antioxidant catalase, which was immunohistochemically identified in neurons throughout the nTS. Thus, H2O2 initially reduces excitability of nTS neurons that is followed by sustained hyperexcitability, which may play a profound role in cardiorespiratory reflexes. PMID:24397952

  16. Precision of Discrete and Rhythmic Forelimb Movements Requires a Distinct Neuronal Subpopulation in the Interposed Anterior Nucleus

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    Aloysius Y.T. Low

    2018-02-01

    Full Text Available The deep cerebellar nuclei (DCN represent output channels of the cerebellum, and they transmit integrated sensorimotor signals to modulate limb movements. But the functional relevance of identifiable neuronal subpopulations within the DCN remains unclear. Here, we examine a genetically tractable population of neurons in the mouse interposed anterior nucleus (IntA. We show that these neurons represent a subset of glutamatergic neurons in the IntA and constitute a specific element of an internal feedback circuit within the cerebellar cortex and cerebello-thalamo-cortical pathway associated with limb control. Ablation and optogenetic stimulation of these neurons disrupt efficacy of skilled reach and locomotor movement and reveal that they control positioning and timing of the forelimb and hindlimb. Together, our findings uncover the function of a distinct neuronal subpopulation in the deep cerebellum and delineate the anatomical substrates and kinematic parameters through which it modulates precision of discrete and rhythmic limb movements.

  17. Estradiol upregulates progesterone receptor and orphanin FQ colocalization in arcuate nucleus neurons and opioid receptor-like receptor-1 expression in proopiomelanocortin neurons that project to the medial preoptic nucleus in the female rat

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    Sanathara, Nayna M.; Moreas, Justine; Mahavongtrakul, Matthew; Sinchak, Kevin

    2014-01-01

    Background Ovarian steroids regulate sexual receptivity in the female rat by acting on neurons that converge on proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARH) that project to the medial preoptic nucleus (MPN). Estradiol rapidly activates these neurons to release β-endorphin that activates MPN μ-opioid receptors (MOP) to inhibit lordosis. Lordosis is facilitated by the subsequent action of progesterone that deactivates the estradiol-induced MPN MOP activation. Orphanin FQ (OFQ/N; aka nociceptin) infusions into the ARH, like progesterone, deactivate MPN MOP and facilitate lordosis in estradiol-primed rats. OFQ/N reduces the activity of ARH β-endorphin neurons through post- and presynaptic mechanisms via its cognate receptor, ORL-1. Methods We tested the hypotheses that progesterone receptors (PR) are expressed in ARH OFQ/N neurons by immunohistochemistry and ORL-1 is expressed in POMC neurons that project to the MPN by combining Fluoro-Gold injection into the MPN and double-label fluorescent in situ hybridization (FISH). We also hypothesized that estradiol increases coexpression of PR-OFQ/N and ORL-1-POMC in ARH neurons of ovariectomized rats. Results The number of PR and OFQ/N immunopositive ARH neurons was increased as was their colocalization by estradiol treatment. FISH for ORL-1 and POMC mRNA revealed a subpopulation of ARH neurons that was triple-labeled indicating these neurons project to the MPN and coexpress ORL-1 and POMC mRNA. Estradiol was shown to upregulate ORL-1 and POMC expression in MPN-projecting ARH neurons. Conclusion Estradiol upregulates the ARH OFQ/N-ORL-1 system projecting to the MPN that regulates lordosis. PMID:24821192

  18. Effects of nitric oxide on magnocellular neurons of the supraoptic nucleus involve multiple mechanisms

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    M.P. da Silva

    2014-02-01

    Full Text Available Physiological evidence indicates that the supraoptic nucleus (SON is an important region for integrating information related to homeostasis of body fluids. Located bilaterally to the optic chiasm, this nucleus is composed of magnocellular neurosecretory cells (MNCs responsible for the synthesis and release of vasopressin and oxytocin to the neurohypophysis. At the cellular level, the control of vasopressin and oxytocin release is directly linked to the firing frequency of MNCs. In general, we can say that the excitability of these cells can be controlled via two distinct mechanisms: 1 the intrinsic membrane properties of the MNCs themselves and 2 synaptic input from circumventricular organs that contain osmosensitive neurons. It has also been demonstrated that MNCs are sensitive to osmotic stimuli in the physiological range. Therefore, the study of their intrinsic membrane properties became imperative to explain the osmosensitivity of MNCs. In addition to this, the discovery that several neurotransmitters and neuropeptides can modulate their electrical activity greatly increased our knowledge about the role played by the MNCs in fluid homeostasis. In particular, nitric oxide (NO may be an important player in fluid balance homeostasis, because it has been demonstrated that the enzyme responsible for its production has an increased activity following a hypertonic stimulation of the system. At the cellular level, NO has been shown to change the electrical excitability of MNCs. Therefore, in this review, we focus on some important points concerning nitrergic modulation of the neuroendocrine system, particularly the effects of NO on the SON.

  19. [Digital signal processing of a novel neuron discharge model stimulation strategy for cochlear implants].

    Science.gov (United States)

    Yang, Yiwei; Xu, Yuejin; Miu, Jichang; Zhou, Linghong; Xiao, Zhongju

    2012-10-01

    To apply the classic leakage integrate-and-fire models, based on the mechanism of the generation of physiological auditory stimulation, in the information processing coding of cochlear implants to improve the auditory result. The results of algorithm simulation in digital signal processor (DSP) were imported into Matlab for a comparative analysis. Compared with CIS coding, the algorithm of membrane potential integrate-and-fire (MPIF) allowed more natural pulse discharge in a pseudo-random manner to better fit the physiological structures. The MPIF algorithm can effectively solve the problem of the dynamic structure of the delivered auditory information sequence issued in the auditory center and allowed integration of the stimulating pulses and time coding to ensure the coherence and relevance of the stimulating pulse time.

  20. Identification of different types of respiratory neurones in the dorsal brainstem nucleus tractus solitarius of the rat

    NARCIS (Netherlands)

    Subramanian, Hari H.; Chow, Chin Moi; Balnave, Ron J.

    2007-01-01

    In Nembutal anaesthetised, spontaneously breathing rats, stereotaxic mapping of the nucleus tractus solitarius (NTS) for respiratory neuronal activity was undertaken. Eight different types of respiratory cells were found between 0.25 and 1.5 mm lateral to midline, extending 0.5 mm caudal to 1.5 mm

  1. Collective behaviors of suprachiasm nucleus neurons under different light—dark cycles

    International Nuclear Information System (INIS)

    Gu Chang-Gui; Liu Zong-Hua; Zhang Xin-Hua

    2014-01-01

    The principal circadian clock in the suprachiasm nucleus (SCN) regulates the circadian rhythm of physiological and behavioral activities of mammals. Except for the normal function of the circadian rhythm, the ensemble of SCN neurons may show two collective behaviors, i.e., a free running period in the absence of a light—dark cycle and an entrainment ability to an external T cycle. Experiments show that both the free running periods and the entrainment ranges may vary from one species to another and can be seriously influenced by the coupling among the SCN neurons. We here review the recent progress on how the heterogeneous couplings influence these two collective behaviors. We will show that in the case of homogeneous coupling, the free running period increases monotonically while the entrainment range decreases monotonically with the increase of the coupling strength. While in the case of heterogenous coupling, the dispersion of the coupling strength plays a crucial role. It has been found that the free running period decreases with the increase of the dispersion while the entrainment ability is enhanced by the dispersion. These findings provide new insights into the mechanism of the circadian clock in the SCN. (topical review - statistical physics and complex systems)

  2. Cochlear implantation in a bilateral Mondini dysplasia.

    Science.gov (United States)

    Turrini, M; Orzan, E; Gabana, M; Genovese, E; Arslan, E; Fisch, U

    1997-01-01

    We report the speech perception progress and programming procedures of a case of congenital profound deafness and bilateral Mondini dysplasia implanted with a Nucleus 20 + 2 cochlear implant at the age of six. Unclear relations between electrodes array and cochlear partition made implant programming difficult and non-standard procedures were set. Cochlear implantation may give excellent rehabilitative results also in cochleae with malformation.

  3. Clonidine, an alpha2-receptor agonist, diminishes GABAergic neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Philbin, Kerry E; Bateman, Ryan J; Mendelowitz, David

    2010-08-06

    In hypertension, there is an autonomic imbalance in which sympathetic activity dominates over parasympathetic control. Parasympathetic activity to the heart originates from cardiac vagal neurons located in the nucleus ambiguus. Presympathetic neurons that project to sympathetic neurons in the spinal cord are located in the ventral brainstem in close proximity to cardiac vagal neurons, and many of these presympathetic neurons are catecholaminergic. In addition to their projection to the spinal cord, many of these presympathetic neurons have axon collaterals that arborize into neighboring cardiorespiratory locations and likely release norepinephrine onto nearby neurons. Activation of alpha(2)-adrenergic receptors in the central nervous system evokes a diverse range of physiological effects, including reducing blood pressure. This study tests whether clonidine, an alpha(2)-adrenergic receptor agonist, alters excitatory glutamatergic, and/or inhibitory GABAergic or glycinergic synaptic neurotransmission to cardiac vagal neurons in the nucleus ambiguus. Cardiac vagal neurons were identified in an in vitro brainstem slice preparation, and synaptic events were recording using whole cell voltage clamp methodologies. Clonidine significantly inhibited GABAergic neurotransmission but had no effect on glycinergic or glutamatergic pathways to cardiac vagal neurons. This diminished inhibitory GABAergic neurotransmission to cardiac vagal neurons would increase parasympathetic activity to the heart, decreasing heart rate and blood pressure. The results presented here provide a cellular substrate for the clinical use of clonidine as a treatment for hypertension as well as a role in alleviating posttraumatic stress disorder by evoking an increase in parasympathetic cardiac vagal activity, and a decrease in heart rate and blood pressure. Copyright 2010 Elsevier B.V. All rights reserved.

  4. Effect of Electroacupuncture at ST36 on Gastric-Related Neurons in Spinal Dorsal Horn and Nucleus Tractus Solitarius

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    Xiaoyu Wang

    2013-01-01

    Full Text Available The aim of this study was to observe the effect of electroacupuncture (EA at the ST36 acupoint on the firing rate of gastric-related neurons in the spinal dorsal horn (SDH and nucleus tractus solitarius (NTS. There were different effects of gastric distention in SDH and NTS in 46 male Sprague-Dawley rats. In 10 excitatory neurons in SDH, most of the neurons were inhibited by homolateral EA. The firing rates decreased significantly (P<0.05 in 10 excitatory gastric-related neurons in NTS; the firing rates of 6 neurons were further excited by homolateral EA, with a significant increase of the firing rates (P<0.05; all inhibitory gastric-related neurons in NTS were excited by EA. The inhibition rate of homolateral EA was significantly increased in comparison with contralateral EA in gastric-related neurons of SDH (P<0.05. There was no significant difference between homolateral and contralateral EA in gastric-related neurons of NTS. EA at ST36 changes the firing rate of gastric-related neurons in SDH and NTS. However, there are some differences in responsive mode in these neurons. The existence of these differences could be one of the physiological foundations of diversity and complexity in EA effects.

  5. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents.

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    Mario Perello

    Full Text Available The adipocyte-derived hormone leptin acts in the brain to reduce body weight and fat mass. Recent studies suggest that parvocellular oxytocin (OXT neurons of the hypothalamic paraventricular nucleus (PVN can mediate body weight reduction through inhibition of food intake and increased energy expenditure. However, the role of OXT neurons of the PVN as a primary target of leptin has not been investigated. Here, we studied the potential role of OXT neurons of the PVN in leptin-mediated effects on body weight regulation in fasted rats. We demonstrated that intracerebroventricular (ICV leptin activates STAT3 phosphorylation in OXT neurons of the PVN, showed that this occurs in a subpopulation of OXT neurons that innervate the nucleus of the solitary tract (NTS, and provided further evidence suggesting a role of OXT to mediate leptin's actions on body weight. In addition, our results indicated that OXT neurons are responsive to ICV leptin and mediate leptin effects on body weight in diet induced obese (DIO rats, which are resistant to the anorectic effects of the hormone. Thus, we conclude that leptin targets a specific subpopulation of parvocellular OXT neurons of the PVN, and that this action may be important for leptin's ability to reduce body weight in both control and obese rats.

  6. DNA damage and cell cycle events implicate cerebellar dentate nucleus neurons as targets of Alzheimer's disease

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    Yang Yan

    2010-12-01

    Full Text Available Abstract Background Although the cerebellum is considered to be predominantly involved in fine motor control, emerging evidence documents its participation in language, impulsive behavior and higher cognitive functions. While the specific connections of the cerebellar deep nuclei (CDN that are responsible for these functions are still being worked out, their deficiency has been termed "cerebellar cognitive affective syndrome" - a syndrome that bears a striking similarity to many of the symptoms of Alzheimer's disease (AD. Using ectopic cell cycle events and DNA damage markers as indexes of cellular distress, we have explored the neuropathological involvement of the CDN in human AD. Results We examined the human cerebellar dentate nucleus in 22 AD cases and 19 controls for the presence of neuronal cell cycle events and DNA damage using immunohistochemistry and fluorescence in situ hybridization. Both techniques revealed several instances of highly significant correlations. By contrast, neither amyloid plaque nor neurofibrillary tangle pathology was detected in this region, consistent with previous reports of human cerebellar pathology. Five cases of early stage AD were examined and while cell cycle and DNA damage markers were well advanced in the hippocampus of all five, few indicators of either cell cycle events (1 case or a DNA damage response (1 case were found in CDN. This implies that CDN neurons are most likely affected later in the course of AD. Clinical-pathological correlations revealed that cases with moderate to high levels of cell cycle activity in their CDN are highly likely to show deficits in unorthodox cerebellar functions including speech, language and motor planning. Conclusion Our results reveal that the CDN neurons are under cellular stress in AD and suggest that some of the non-motor symptoms found in patients with AD may be partly cerebellar in origin.

  7. Development of GPCR modulation of GABAergic transmission in chicken nucleus laminaris neurons.

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    Zheng-Quan Tang

    Full Text Available Neurons in the nucleus laminaris (NL of birds act as coincidence detectors and encode interaural time difference to localize the sound source in the azimuth plane. GABAergic transmission in a number of CNS nuclei including the NL is subject to a dual modulation by presynaptic GABA(B receptors (GABA(BRs and metabotropic glutamate receptors (mGluRs. Here, using in vitro whole-cell patch clamp recordings from acute brain slices of the chick, we characterized the following important but unknown properties pertaining to such a dual modulation: (1 emergence of functional GABA synapses in NL neurons; (2 the temporal onset of neuromodulation mediated by GABA(BRs and mGluRs; and (3 the physiological conditions under which GABA(BRs and mGluRs are activated by endogenous transmitters. We found that (1 GABA(AR-mediated synaptic responses were observed in about half of the neurons at embryonic day 11 (E11; (2 GABA(BR-mediated modulation of the GABAergic transmission was detectable at E11, whereas the modulation by mGluRs did not emerge until E15; and (3 endogenous activity of GABA(BRs was induced by both low- (5 or 10 Hz and high-frequency (200 Hz stimulation of the GABAergic pathway, whereas endogenous activity of mGluRs was induced by high- (200 Hz but not low-frequency (5 or 10 Hz stimulation of the glutamatergic pathway. Furthermore, the endogenous activity of mGluRs was mediated by group II but not group III members. Therefore, autoreceptor-mediated modulation of GABAergic transmission emerges at the same time when the GABA synapses become functional. Heteroreceptor-mediated modulation appears at a later time and is receptor type dependent in vitro.

  8. Distribution and compartmental organization of GABAergic medium-sized spiny neurons in the mouse Nucleus Accumbens

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    Giuseppe eGangarossa

    2013-02-01

    Full Text Available The nucleus accumbens (NAc is a critical brain region involved in many reward-related behaviors. The NAc comprises major compartments the core and the shell, which encompass several subterritories. GABAergic medium-sized spiny neurons (MSNs constitute the output neurons of the NAc core and shell. While the functional organization of the NAc core outputs resembles the one described for the dorsal striatum, a simple classification of the NAc shell neurons has been difficult to define due to the complexity of the compartmental segregation of cells. We used a variety of BAC transgenic mice expressing enhanced green fluorescence (EGFP or the Cre-recombinase (Cre under the control of the promoter of dopamine D1, D2, and D3 receptors and of adenosine A2a receptor to dissect the microanatomy of the NAc. Moreover, using various immunological markers we characterized in detail the distribution of MSNs in the mouse NAc. In addition, cell-type specific ERK phosphorylation in the NAc subterritories was analyzed following acute administration of SKF81297 (a D1R-like agonist, quinpirole (a D2R-like agonist, apomorphine (a non-selective DA receptor agonist, raclopride (a D2R-like antagonist, and psychostimulant drugs, including cocaine and d-amphetamine. Each drug generated a unique topography and cell-type specific activation of ERK in the NAc. Our results show the existence of marked differences in the receptor expression pattern and functional activation of MSNs within the shell subterritories. This study emphasizes the anatomical and functional heterogeneity of the NAc, which will have to be considered in its further study.

  9. Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

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    Changying Ling

    Full Text Available The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2. Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4 µm(2. Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

  10. Urotensin II promotes vagal-mediated bradycardia by activating cardiac-projecting parasympathetic neurons of nucleus ambiguus.

    Science.gov (United States)

    Brailoiu, Gabriela Cristina; Deliu, Elena; Rabinowitz, Joseph E; Tilley, Douglas G; Koch, Walter J; Brailoiu, Eugen

    2014-05-01

    Urotensin II (U-II) is a cyclic undecapeptide that regulates cardiovascular function at central and peripheral sites. The functional role of U-II nucleus ambiguus, a key site controlling cardiac tone, has not been established, despite the identification of U-II and its receptor at this level. We report here that U-II produces an increase in cytosolic Ca(2+) concentration in retrogradely labeled cardiac vagal neurons of nucleus ambiguus via two pathways: (i) Ca(2+) release from the endoplasmic reticulum via inositol 1,4,5-trisphosphate receptor; and (ii) Ca(2+) influx through P/Q-type Ca(2+) channels. In addition, U-II depolarizes cultured cardiac parasympathetic neurons. Microinjection of increasing concentrations of U-II into nucleus ambiguus elicits dose-dependent bradycardia in conscious rats, indicating the in vivo activation of the cholinergic pathway controlling the heart rate. Both the in vitro and in vivo effects were abolished by the urotensin receptor antagonist, urantide. Our findings suggest that, in addition, to the previously reported increase in sympathetic outflow, U-II activates cardiac vagal neurons of nucleus ambiguus, which may contribute to cardioprotection. © 2014 International Society for Neurochemistry.

  11. Nucleus accumbens neurons encode Pavlovian approach behaviors: evidence from an autoshaping paradigm.

    Science.gov (United States)

    Day, Jeremy J; Wheeler, Robert A; Roitman, Mitchell F; Carelli, Regina M

    2006-03-01

    Environmental stimuli predictive of appetitive events can elicit Pavlovian approach responses that enhance an organism's ability to track and secure natural rewards, but may also contribute to the compulsive nature of drug addiction. Here, we examined the activity of individual nucleus accumbens (NAc) neurons during an autoshaping paradigm. One conditioned stimulus (CS+, a retractable lever presented for 10 s) was immediately followed by the delivery of a 45-mg sucrose pellet to a food receptacle, while another stimulus (CS-, a separate retractable lever presented for 10 s) was never followed by sucrose. Approach responses directed at the CS+ and CS- were recorded as lever presses and had no experimental consequence. Rats (n = 9) selectively approached the CS+ on more than 80% of trials and were surgically prepared for electrophysiological recording. Of 76 NAc neurons, 57 cells (75%) exhibited increases and/or decreases in firing rate (i.e. termed 'phasically active') during the CS+ presentation and corresponding approach response. Forty-seven percent of phasically active cells (27 out of 57) were characterized by time-locked but transient increases in cell firing, while 53% (30 out of 57) showed a significant reduction in firing for the duration of the CS+. In contrast, the same excitatory subpopulation exhibited smaller increases in activity relative to CS- onset, while the inhibitory subpopulation showed no change in firing during the CS- period. The magnitude and prevalence of cue-related neural responses reported here indicates that the NAc encodes biologically significant, repetitive approach responses that may model the compulsive nature of drug addiction in humans.

  12. Organization of Functional Long-Range Circuits Controlling the Activity of Serotonergic Neurons in the Dorsal Raphe Nucleus.

    Science.gov (United States)

    Zhou, Li; Liu, Ming-Zhe; Li, Qing; Deng, Juan; Mu, Di; Sun, Yan-Gang

    2017-03-21

    Serotonergic neurons play key roles in various biological processes. However, circuit mechanisms underlying tight control of serotonergic neurons remain largely unknown. Here, we systematically investigated the organization of long-range synaptic inputs to serotonergic neurons and GABAergic neurons in the dorsal raphe nucleus (DRN) of mice with a combination of viral tracing, slice electrophysiological, and optogenetic techniques. We found that DRN serotonergic neurons and GABAergic neurons receive largely comparable synaptic inputs from six major upstream brain areas. Upon further analysis of the fine functional circuit structures, we found both bilateral and ipsilateral patterns of topographic connectivity in the DRN for the axons from different inputs. Moreover, the upstream brain areas were found to bidirectionally control the activity of DRN serotonergic neurons by recruiting feedforward inhibition or via a push-pull mechanism. Our study provides a framework for further deciphering the functional roles of long-range circuits controlling the activity of serotonergic neurons in the DRN. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Type I vs type II spiral ganglion neurons exhibit differential survival and neuritogenesis during cochlear development

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    Housley Gary D

    2011-10-01

    Full Text Available Abstract Background The mechanisms that consolidate neural circuitry are a major focus of neuroscience. In the mammalian cochlea, the refinement of spiral ganglion neuron (SGN innervation to the inner hair cells (by type I SGNs and the outer hair cells (by type II SGNs is accompanied by a 25% loss of SGNs. Results We investigated the segregation of neuronal loss in the mouse cochlea using β-tubulin and peripherin antisera to immunolabel all SGNs and selectively type II SGNs, respectively, and discovered that it is the type II SGN population that is predominately lost within the first postnatal week. Developmental neuronal loss has been attributed to the decline in neurotrophin expression by the target hair cells during this period, so we next examined survival of SGN sub-populations using tissue culture of the mid apex-mid turn region of neonatal mouse cochleae. In organotypic culture for 48 hours from postnatal day 1, endogenous trophic support from the organ of Corti proved sufficient to maintain all type II SGNs; however, a large proportion of type I SGNs were lost. Culture of the spiral ganglion as an explant, with removal of the organ of Corti, led to loss of the majority of both SGN sub-types. Brain-derived neurotrophic factor (BDNF added as a supplement to the media rescued a significant proportion of the SGNs, particularly the type II SGNs, which also showed increased neuritogenesis. The known decline in BDNF production by the rodent sensory epithelium after birth is therefore a likely mediator of type II neuron apoptosis. Conclusion Our study thus indicates that BDNF supply from the organ of Corti supports consolidation of type II innervation in the neonatal mouse cochlea. In contrast, type I SGNs likely rely on additional sources for trophic support.

  14. Neurons in the thalamic reticular nucleus are selective for diverse and complex visual features

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    Vishal eVaingankar

    2012-12-01

    Full Text Available All visual signals the cortex receives are influenced by the perigeniculate sector of the thalamic reticular nucleus, which receives input from relay cells in the lateral geniculate and provides feedback inhibition in return. Relay cells have been studied in quantitative depth; they behave in a roughly linear fashion and have receptive fields with a stereotyped centre-surround structure. We know far less about reticular neurons. Qualitative studies indicate they simply pool ascending input to generate nonselective gain control. Yet the perigeniculate is complicated; local cells are densely interconnected and fire lengthy bursts. Thus, we employed quantitative methods to explore the perigeniculate, using relay cells as controls. By adapting methods of spike-triggered averaging and covariance analysis for bursts, we identified both first and second order features that build reticular receptive fields. The shapes of these spatiotemporal subunits varied widely; no stereotyped pattern emerged. Companion experiments showed that the shape of the first but not second order features could be explained by the overlap of On and Off inputs to a given cell. Moreover, we assessed the predictive power of the receptive field and how much information each component subunit conveyed. Linear-nonlinear models including multiple subunits performed better than those made with just one; further each subunit encoded different visual information. Model performance for reticular cells was always lesser than for relay cells, however, indicating that reticular cells process inputs nonlinearly. All told, our results suggest that the perigeniculate encodes diverse visual features to selectively modulate activity transmitted downstream

  15. Effects of GABA microinjection into dorsal raphe nucleus on behavior and activity of lateral habenular neurons in mice.

    Science.gov (United States)

    Xiao, Jinyu; Song, Meiying; Li, Fengdan; Liu, Xiaofeng; Anwar, Alinur; Zhao, Hua

    2017-12-01

    The dorsal raphe nucleus (DRN) is a key site for 5-hydroxytryptamine (5-HT) synthesis and release. DRN dysfunction has been implicated in several stress-related disorders, including depression and anxiety. The lateral habenular nucleus (LHb) has been shown to inhibit the activity of DRN 5-HT neurons, and thus the LHb-DRN pathway plays an important role in the pathogenesis of depression. Although it is known that the LHb also receives the projection from the 5-HT neuron in the DRN, whether 5-HT neurons in the DRN can influence activity of the LHb in vivo and whether this effect is related to the induced behavioral changes have not been investigated. In the current study, we determined how injecting γ-aminobutyric acid (GABA) into the DRN to inhibit 5-HT neurons affected behavior and the changes in the activity of LHb neurons in mice. We found that GABA injection into the DRN induced depression-like behavior in mice, as indicated by increased immobility time, and decreased climbing time in the forced swimming test and the tail suspension test, decreased time spent in the center and total distance moved in the open field test. Using extracellular single unit recording, we showed that the firing rate of LHb neurons decreased after GABA microinjection into the DRN. Further, c-Fos expression in LHb neurons was inhibited. Together our results indicate that inhibition of DRN 5-HT neurons can cause decreased LHb activity and depression-like behavior in mice, however this depression-like behavior could be independent of the LHb activity. The observed decrease in LHb activity is probably due to the presence of a negative feedback loop between the DRN and the LHb, which may play a role in maintaining emotional homeostasis. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Anxiogenic drug administration and elevated plus-maze exposure in rats activate populations of relaxin-3 neurons in the nucleus incertus and serotonergic neurons in the dorsal raphe nucleus.

    Science.gov (United States)

    Lawther, A J; Clissold, M L; Ma, S; Kent, S; Lowry, C A; Gundlach, A L; Hale, M W

    2015-09-10

    Anxiety is a complex and adaptive emotional state controlled by a distributed and interconnected network of brain regions, and disruption of these networks is thought to give rise to the behavioral symptoms associated with anxiety disorders in humans. The dorsal raphe nucleus (DR), which contains the majority of forebrain-projecting serotonergic neurons, is implicated in the control of anxiety states and anxiety-related behavior via neuromodulatory effects on these networks. Relaxin-3 is the native neuropeptide ligand for the Gi/o-protein-coupled receptor, RXFP3, and is primarily expressed in the nucleus incertus (NI), a tegmental region immediately caudal to the DR. RXFP3 activation has been shown to modulate anxiety-related behavior in rodents, and RXFP3 mRNA is expressed in the DR. In this study, we examined the response of relaxin-3-containing neurons in the NI and serotonergic neurons in the DR following pharmacologically induced anxiety and exposure to an aversive environment. We administered the anxiogenic drug FG-7142 or vehicle to adult male Wistar rats and, 30 min later, exposed them to either the elevated plus-maze or home cage control conditions. Immunohistochemical detection of c-Fos was used to determine activation of serotonergic neurons in the DR and relaxin-3 neurons in the NI, measured 2h following drug injection. Analysis revealed that FG-7142 administration and exposure to the elevated plus-maze are both associated with an increase in c-Fos expression in relaxin-3-containing neurons in the NI and in serotonergic neurons in dorsal and ventrolateral regions of the DR. These data are consistent with the hypothesis that relaxin-3 systems in the NI and serotonin systems in the DR interact to form part of a network involved in the control of anxiety-related behavior. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Evidence for role of acid-sensing ion channels in nucleus ambiguus neurons: essential differences in anesthetized versus awake rats.

    Science.gov (United States)

    Brailoiu, G Cristina; Deliu, Elena; Altmann, Joseph B; Chitravanshi, Vineet; Brailoiu, Eugen

    2014-08-01

    Acid-sensing ion channels (ASIC) are widely expressed in several brain regions including medulla; their role in physiology and pathophysiology is incompletely understood. We examined the effect of acidic pH of 6.2 on the medullary neurons involved in parasympathetic cardiac control. Our results indicate that retrogradely labeled cardiac vagal neurons of nucleus ambiguus are depolarized by acidic pH. In addition, acidic saline of pH 6.2 increases cytosolic Ca(2+) concentration by promoting Ca(2+) influx in nucleus ambiguus neurons. In vivo studies indicate that microinjection of acidic artificial cerebrospinal fluid (pH 6.2) into the nucleus ambiguus decreases the heart rate in conscious rats, whereas it has no effect in anesthetized animals. Pretreatment with either amiloride or benzamil, two widely used ASIC blockers, abolishes both the in vitro and in vivo effects elicited by pH 6.2. Our findings support a critical role for ASIC in modulation of cardiac vagal tone and provide a potential mechanism for acidosis-induced bradycardia, while identifying important differences in the response to acidic pH between anesthetized and conscious rats.

  18. Angiotensin Type-2 Receptors Influence the Activity of Vasopressin Neurons in the Paraventricular Nucleus of the Hypothalamus in Male Mice.

    Science.gov (United States)

    de Kloet, Annette D; Pitra, Soledad; Wang, Lei; Hiller, Helmut; Pioquinto, David J; Smith, Justin A; Sumners, Colin; Stern, Javier E; Krause, Eric G

    2016-08-01

    It is known that angiotensin-II acts at its type-1 receptor to stimulate vasopressin (AVP) secretion, which may contribute to angiotensin-II-induced hypertension. Less well known is the impact of angiotensin type-2 receptor (AT2R) activation on these processes. Studies conducted in a transgenic AT2R enhanced green fluorescent protein reporter mouse revealed that although AT2R are not themselves localized to AVP neurons within the paraventricular nucleus of the hypothalamus (PVN), they are localized to neurons that extend processes into the PVN. In the present set of studies, we set out to characterize the origin, phenotype, and function of nerve terminals within the PVN that arise from AT2R-enhanced green fluorescent protein-positive neurons and synapse onto AVP neurons. Initial experiments combined genetic and neuroanatomical techniques to determine that γ-aminobutyric acid (GABA)ergic neurons derived from the peri-PVN area containing AT2R make appositions onto AVP neurons within the PVN, thereby positioning AT2R to negatively regulate neuroendocrine secretion. Subsequent patch-clamp electrophysiological experiments revealed that selective activation of AT2R in the peri-PVN area using compound 21 facilitates inhibitory (ie, GABAergic) neurotransmission and leads to reduced activity of AVP neurons within the PVN. Final experiments determined the functional impact of AT2R activation by testing the effects of compound 21 on plasma AVP levels. Collectively, these experiments revealed that AT2R expressing neurons make GABAergic synapses onto AVP neurons that inhibit AVP neuronal activity and suppress baseline systemic AVP levels. These findings have direct implications in the targeting of AT2R for disorders of AVP secretion and also for the alleviation of high blood pressure.

  19. Spatiotemporal profiles of receptive fields of neurons in the lateral posterior nucleus of the cat LP-pulvinar complex.

    Science.gov (United States)

    Piché, Marilyse; Thomas, Sébastien; Casanova, Christian

    2015-10-01

    The pulvinar is the largest extrageniculate thalamic visual nucleus in mammals. It establishes reciprocal connections with virtually all visual cortexes and likely plays a role in transthalamic cortico-cortical communication. In cats, the lateral posterior nucleus (LP) of the LP-pulvinar complex can be subdivided in two subregions, the lateral (LPl) and medial (LPm) parts, which receive a predominant input from the striate cortex and the superior colliculus, respectively. Here, we revisit the receptive field structure of LPl and LPm cells in anesthetized cats by determining their first-order spatiotemporal profiles through reverse correlation analysis following sparse noise stimulation. Our data reveal the existence of previously unidentified receptive field profiles in the LP nucleus both in space and time domains. While some cells responded to only one stimulus polarity, the majority of neurons had receptive fields comprised of bright and dark responsive subfields. For these neurons, dark subfields' size was larger than that of bright subfields. A variety of receptive field spatial organization types were identified, ranging from totally overlapped to segregated bright and dark subfields. In the time domain, a large spectrum of activity overlap was found, from cells with temporally coinciding subfield activity to neurons with distinct, time-dissociated subfield peak activity windows. We also found LP neurons with space-time inseparable receptive fields and neurons with multiple activity periods. Finally, a substantial degree of homology was found between LPl and LPm first-order receptive field spatiotemporal profiles, suggesting a high integration of cortical and subcortical inputs within the LP-pulvinar complex. Copyright © 2015 the American Physiological Society.

  20. Age-related changes in functional postsynaptic nicotinic acetylcholine receptor subunits in neurons of the laterodorsal tegmental nucleus, a nucleus important in drug addiction.

    Science.gov (United States)

    Christensen, Mark H; Kohlmeier, Kristi A

    2016-03-01

    The earlier an individual initiates cigarette smoking, the higher the likelihood of development of dependency to nicotine, the addictive ingredient in cigarettes. One possible mechanism underlying this higher addiction liability is an ontogenetically differential cellular response induced by nicotine in neurons mediating the reinforcing or euphoric effects of this drug, which could arise from age-related differences in the composition of nicotinic acetylcholine receptor (nAChR) subunits. In the current study, we examined whether the subunit composition of nAChRs differed between neurons within the laterodorsal tegmentum (LDT), a nucleus importantly involved in drug addiction associated behaviours, across two periods of ontogeny in which nicotine-mediated excitatory responses were shown to depend on age. To this end, whole-cell patch-clamp recordings in mouse brain slices from identified LDT neurons, in combination with nAChR subunit-specific receptor antagonists, were conducted. Comparison of the contribution of different nAChR subunits to acetylcholine (ACh)-induced inward currents indicated that the contributions of the β2 and/or β4 and α7 nAChR subunits alter across age. Taken together, we conclude that across a limited ontogenetic period, there is plasticity in the subunit composition of nAChRs in LDT neurons. In addition, our data indicate, for the first time, functional presence of α6 nAChR subunits in LDT neurons within the age ranges studied. Changes in subunit composition of nAChRs across ontogeny could contribute to the age-related differential excitability induced by nicotine. Differences in the subunit composition of nAChRs within the LDT would be expected to contribute to ontogenetic-dependent outflow from the LDT to target regions, which include reward-related circuitry. © 2014 Society for the Study of Addiction.

  1. β adrenergic receptor modulation of neurotransmission to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Bateman, R J; Boychuk, C R; Philbin, K E; Mendelowitz, D

    2012-05-17

    β-adrenergic receptors are a class of G protein-coupled receptors that have essential roles in regulating heart rate, blood pressure, and other cardiorespiratory functions. Although the role of β adrenergic receptors in the peripheral nervous system is well characterized, very little is known about their role in the central nervous system despite being localized in many brain regions involved in autonomic activity and regulation. Since parasympathetic activity to the heart is dominated by cardiac vagal neurons (CVNs) originating in the nucleus ambiguus (NA), β adrenergic receptors localized in the NA represent a potential target for modulating cardiac vagal activity and heart rate. This study tests the hypothesis that activation of β adrenergic receptors alters the membrane properties and synaptic neurotransmission to CVNs. CVNs were identified in brainstem slices, and membrane properties and synaptic events were recorded using the whole-cell voltage-clamp technique. The nonselective β agonist isoproterenol significantly decreased inhibitory GABAergic and glycinergic as well as excitatory glutamatergic neurotransmission to CVNs. In addition, the β(1)-selective receptor agonist dobutamine, but not β(2) or β(3) receptor agonists, significantly decreased inhibitory GABAergic and glycinergic and excitatory glutamatergic neurotransmission to CVNs. These decreases in neurotransmission to CVNs persisted in the presence of tetrodotoxin (TTX). These results provide a mechanism by which activation of adrenergic receptors in the brainstem can alter parasympathetic activity to the heart. Likely physiological roles for this adrenergic receptor activation are coordination of parasympathetic-sympathetic activity and β receptor-mediated increases in heart rate upon arousal. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.

    Science.gov (United States)

    Hachem-Delaunay, Sabira; Fournier, Marie-Line; Cohen, Candie; Bonneau, Nicolas; Cador, Martine; Baunez, Christelle; Le Moine, Catherine

    2015-08-01

    The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long-Evans rats were subjected to STN HFS (130 Hz, 60 μs, 50-150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Neurons in the thalamic reticular nucleus are selective for diverse and complex visual features

    Science.gov (United States)

    Vaingankar, Vishal; Soto-Sanchez, Cristina; Wang, Xin; Sommer, Friedrich T.; Hirsch, Judith A.

    2012-01-01

    All visual signals the cortex receives are influenced by the perigeniculate sector (PGN) of the thalamic reticular nucleus, which receives input from relay cells in the lateral geniculate and provides feedback inhibition in return. Relay cells have been studied in quantitative depth; they behave in a roughly linear fashion and have receptive fields with a stereotyped center-surround structure. We know far less about reticular neurons. Qualitative studies indicate they simply pool ascending input to generate non-selective gain control. Yet the perigeniculate is complicated; local cells are densely interconnected and fire lengthy bursts. Thus, we employed quantitative methods to explore the perigeniculate using relay cells as controls. By adapting methods of spike-triggered averaging and covariance analysis for bursts, we identified both first and second order features that build reticular receptive fields. The shapes of these spatiotemporal subunits varied widely; no stereotyped pattern emerged. Companion experiments showed that the shape of the first but not second order features could be explained by the overlap of On and Off inputs to a given cell. Moreover, we assessed the predictive power of the receptive field and how much information each component subunit conveyed. Linear-non-linear (LN) models including multiple subunits performed better than those made with just one; further each subunit encoded different visual information. Model performance for reticular cells was always lesser than for relay cells, however, indicating that reticular cells process inputs non-linearly. All told, our results suggest that the perigeniculate encodes diverse visual features to selectively modulate activity transmitted downstream. PMID:23269915

  4. Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording

    NARCIS (Netherlands)

    Schaap, J.; Bos, N. P.; de Jeu, M. T.; Geurtsen, A. M.; Meijer, J. H.; Pennartz, C. M.

    1999-01-01

    The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological

  5. Role of nucleus of the solitary tract noradrenergic neurons in post-stress cardiovascular and hormonal control in male rats.

    Science.gov (United States)

    Bundzikova-Osacka, Jana; Ghosal, Sriparna; Packard, Benjamin A; Ulrich-Lai, Yvonne M; Herman, James P

    2015-01-01

    Chronic stress causes hypothalamo-pituitary-adrenal (HPA) axis hyperactivity and cardiovascular dyshomeostasis. Noradrenergic (NA) neurons in the nucleus of the solitary tract (NTS) are considered to play a role in these changes. In this study, we tested the hypothesis that NTS NA A2 neurons are required for cardiovascular and HPA axis responses to both acute and chronic stress. Adult male rats received bilateral microinjection into the NTS of 6-hydroxydopamine (6-OHDA) to lesion A2 neurons [cardiovascular study, n = 5; HPA study, n = 5] or vehicle [cardiovascular study, n = 6; HPA study, n = 4]. Rats were exposed to acute restraint stress followed by 14 d of chronic variable stress (CVS). On the last day of testing, rats were placed in a novel elevated plus maze (EPM) to test post-CVS stress responses. Lesions of NTS A2 neurons reduced the tachycardic response to acute restraint, confirming that A2 neurons promote sympathetic activation following acute stress. In addition, CVS increased the ratio of low-frequency to high-frequency power for heart rate variability, indicative of sympathovagal imbalance, and this effect was significantly attenuated by 6-OHDA lesion. Lesions of NTS A2 neurons reduced acute restraint-induced corticosterone secretion, but did not affect the corticosterone response to the EPM, indicating that A2 neurons promote acute HPA axis responses, but are not involved in CVS-mediated HPA axis sensitization. Collectively, these data indicate that A2 neurons promote both cardiovascular and HPA axis responses to acute stress. Moreover, A2 catecholaminergic neurons may contribute to the potentially deleterious enhancement of sympathetic drive following chronic stress.

  6. Precision of Discrete and Rhythmic Forelimb Movements Requires a Distinct Neuronal Subpopulation in the Interposed Anterior Nucleus.

    Science.gov (United States)

    Low, Aloysius Y T; Thanawalla, Ayesha R; Yip, Alaric K K; Kim, Jinsook; Wong, Kelly L L; Tantra, Martesa; Augustine, George J; Chen, Albert I

    2018-02-27

    The deep cerebellar nuclei (DCN) represent output channels of the cerebellum, and they transmit integrated sensorimotor signals to modulate limb movements. But the functional relevance of identifiable neuronal subpopulations within the DCN remains unclear. Here, we examine a genetically tractable population of neurons in the mouse interposed anterior nucleus (IntA). We show that these neurons represent a subset of glutamatergic neurons in the IntA and constitute a specific element of an internal feedback circuit within the cerebellar cortex and cerebello-thalamo-cortical pathway associated with limb control. Ablation and optogenetic stimulation of these neurons disrupt efficacy of skilled reach and locomotor movement and reveal that they control positioning and timing of the forelimb and hindlimb. Together, our findings uncover the function of a distinct neuronal subpopulation in the deep cerebellum and delineate the anatomical substrates and kinematic parameters through which it modulates precision of discrete and rhythmic limb movements. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  7. Overactivity of Liver-Related Neurons in the Paraventricular Nucleus of the Hypothalamus: Electrophysiological Findings in db/db Mice.

    Science.gov (United States)

    Gao, Hong; Molinas, Adrien J R; Miyata, Kayoko; Qiao, Xin; Zsombok, Andrea

    2017-11-15

    Preautonomic neurons in the paraventricular nucleus (PVN) of the hypothalamus play a large role in the regulation of hepatic functions via the autonomic nervous system. Activation of hepatic sympathetic nerves increases glucose and lipid metabolism and contributes to the elevated hepatic glucose production observed in the type 2 diabetic condition. This augmented sympathetic output could originate from altered activity of liver-related PVN neurons. Remarkably, despite the importance of the brain-liver pathway, the cellular properties of liver-related neurons are not known. In this study, we provide the first evidence of overall activity of liver-related PVN neurons. Liver-related PVN neurons were identified with a retrograde, trans-synaptic, viral tracer in male lean and db/db mice and whole-cell patch-clamp recordings were conducted. In db/db mice, the majority of liver-related PVN neurons fired spontaneously; whereas, in lean mice the majority of liver-related PVN neurons were silent, indicating that liver-related PVN neurons are more active in db/db mice. Persistent, tonic inhibition was identified in liver-related PVN neurons; although, the magnitude of tonic inhibitory control was not different between lean and db/db mice. In addition, our study revealed that the transient receptor potential vanilloid type 1-dependent increase of excitatory neurotransmission was reduced in liver-related PVN neurons of db/db mice. These findings demonstrate plasticity of liver-related PVN neurons and a shift toward excitation in a diabetic mouse model. Our study suggests altered autonomic circuits at the level of the PVN, which can contribute to autonomic dysfunction and dysregulation of neural control of hepatic functions including glucose metabolism. SIGNIFICANCE STATEMENT A growing body of evidence suggests the importance of the autonomic control in the regulation of hepatic metabolism, which plays a major role in the development and progression of type 2 diabetes mellitus

  8. Secondhand tobacco smoke exposure differentially alters nucleus tractus solitarius neurons at two different ages in developing non-human primates

    International Nuclear Information System (INIS)

    Sekizawa, Shin-ichi; Joad, Jesse P.; Pinkerton, Kent E.; Bonham, Ann C.

    2010-01-01

    Exposing children to secondhand tobacco smoke (SHS) is associated with increased risk for asthma, bronchiolitis and SIDS. The role for changes in the developing CNS contributing to these problems has not been fully explored. We used rhesus macaques to test the hypothesis that SHS exposure during development triggers neuroplastic changes in the nucleus tractus solitarius (NTS), where lung sensory information related to changes in airway and lung function is first integrated. Pregnant monkeys were exposed to filtered air (FA) or SHS for 6 h/day, 5 days/week starting at 50-day gestational age. Mother/infant pairs continued the exposures postnatally to age 3 or 13 months, which may be equivalent to approximately 1 or 4 years of human age, respectively. Whole-cell recordings were made of second-order NTS neurons in transverse brainstem slices. To target the consequences of SHS exposure based on neuronal subgroups, we classified NTS neurons into two phenotypes, rapid-onset spiking (RS) and delayed-onset spiking (DS), and then evaluated intrinsic and synaptic excitabilities in FA-exposed animals. RS neurons showed greater cell excitability especially at age of 3 months while DS neurons received greater amplitudes of excitatory postsynaptic currents (EPSCs). Developmental neuroplasticity such as increases in intrinsic and synaptic excitabilities were detected especially in DS neurons. In 3 month olds, SHS exposure effects were limited to excitatory changes in RS neurons, specifically increases in evoked EPSC amplitudes and increased spiking responses accompanied by shortened action potential width. By 13 months, the continued SHS exposure inhibited DS neuronal activity; decreases in evoked EPSC amplitudes and blunted spiking responses accompanied by prolonged action potential width. The influence of SHS exposure on age-related and phenotype specific changes may be associated with age-specific respiratory problems, for which SHS exposure can increase the risk, such as SIDS

  9. Acid-sensing ion channels contribute to chemosensitivity of breathing-related neurons of the nucleus of the solitary tract.

    Science.gov (United States)

    Huda, Rafiq; Pollema-Mays, Sarah L; Chang, Zheng; Alheid, George F; McCrimmon, Donald R; Martina, Marco

    2012-10-01

    Cellular mechanisms of central pH chemosensitivity remain largely unknown. The nucleus of the solitary tract (NTS) integrates peripheral afferents with central pathways controlling breathing; NTS neurons function as central chemosensors, but only limited information exists concerning the ionic mechanisms involved. Acid-sensing ion channels (ASICs) mediate chemosensitivity in nociceptive terminals, where pH values ∼6.5 are not uncommon in inflammation, but are also abundantly expressed throughout the brain where pHi s tightly regulated and their role is less clear. Here we test the hypothesis that ASICs are expressed in NTS neurons and contribute to intrinsic chemosensitivity and control of breathing. In electrophysiological recordings from acute rat NTS slices, ∼40% of NTS neurons responded to physiological acidification (pH 7.0) with a transient depolarization. This response was also present in dissociated neurons suggesting an intrinsic mechanism. In voltage clamp recordings in slices, a pH drop from 7.4 to 7.0 induced ASIC-like inward currents (blocked by 100 μM amiloride) in ∼40% of NTS neurons, while at pH ≤ 6.5 these currents were detected in all neurons tested; RT-PCR revealed expression of ASIC1 and, less abundantly, ASIC2 in the NTS. Anatomical analysis of dye-filled neurons showed that ASIC-dependent chemosensitive cells (cells responding to pH 7.0) cluster dorsally in the NTS. Using in vivo retrograde labelling from the ventral respiratory column, 90% (9/10) of the labelled neurons showed an ASIC-like response to pH 7.0, suggesting that ASIC currents contribute to control of breathing. Accordingly, amiloride injection into the NTS reduced phrenic nerve activity of anaesthetized rats with an elevated arterial P(CO(2)) .

  10. Genetic Perturbations Suggest a Role of the Resting Potential in Regulating the Expression of the Ion Channels of the KCNA and HCN families in Octopus Cells of the Ventral Cochlear Nucleus

    Science.gov (United States)

    Cao, Xiao-Jie; Oertel, Donata

    2017-01-01

    Low-voltage-activated K+ (gKL) and hyperpolarization-activated mixed cation conductances (gh) mediate currents, IKL and Ih, through channels of the Kv1 (KCNA) and HCN families respectively and give auditory neurons the temporal precision required for signaling information about the onset, fine structure, and time of arrival of sounds. Being partially activated at rest, gKL and gh contribute to the resting potential and shape responses to even small subthreshold synaptic currents. Resting gKL and gh also affect the coupling of somatic depolarization with the generation of action potentials. To learn how these important conductances are regulated we have investigated how genetic perturbations affect their expression in octopus cells of the ventral cochlear nucleus (VCN). We report five new findings: First, the magnitude of gh and gKL varied over more than two-fold between wild type strains of mice. Second, average resting potentials are not different in different strains of mice even in the face of large differences in average gKL and gh. Third, IKL has two components, one being α-dendrotoxin (α-DTX)-sensitive and partially inactivating and the other being α-DTX-insensitive, tetraethylammonium (TEA)-sensitive, and non-inactivating. Fourth, the loss of Kv1.1 results in diminution of the α-DTX-sensitive IKL, and compensatory increased expression of an α-DTX-insensitive, tetraethylammonium (TEA)-sensitive IKL. Fifth, Ih and IKL are balanced at the resting potential in all wild type and mutant octopus cells even when resting potentials vary in individual cells over nearly 10 mV, indicating that the resting potential influences the expression of gh and gKL. The independence of resting potentials on gKL and gh shows that gKL and gh do not, over days or weeks, determine the resting potential but rather that the resting potential plays a role in regulating the magnitude of either or both gKL and gh. PMID:28065805

  11. Nucleus Accumbens Dopamine D2-Receptor Expressing Neurons Control Behavioral Flexibility in a Place Discrimination Task in the IntelliCage

    Science.gov (United States)

    Macpherson, Tom; Morita, Makiko; Wang, Yanyan; Sasaoka, Toshikuni; Sawa, Akira; Hikida, Takatoshi

    2016-01-01

    Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1- or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated…

  12. Prolonged sound exposure has different effects on increasing neuronal size in the auditory cortex and brainstem

    Czech Academy of Sciences Publication Activity Database

    Lu, H. P.; Syka, Josef; Chiu, T. W.; Poon, P. W. F.

    2014-01-01

    Roč. 314, AUG 2014 (2014), s. 42-50 ISSN 0378-5955 R&D Projects: GA ČR(CZ) GCP303/11/J005; GA ČR(CZ) GAP304/12/1342 Institutional support: RVO:68378041 Keywords : inferior colliculus * cochlear nucleus * neocortical neurons Subject RIV: FH - Neurology Impact factor: 2.968, year: 2014

  13. Identifying cochlear implant channels with poor electrode-neuron interface: electrically-evoked auditory brainstem responses measured with the partial tripolar configuration

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F.; Tremblay, Kelly L.

    2011-01-01

    Objectives The goal of this study was to compare cochlear implant behavioral measures and electrically-evoked auditory brainstem responses (EABRs) obtained with a spatially focused electrode configuration. It has been shown previously that channels with high thresholds, when measured with the tripolar configuration, exhibit relatively broad psychophysical tuning curves (Bierer and Faulkner, 2010). The elevated threshold and degraded spatial/spectral selectivity of such channels are consistent with a poor electrode-neuron interface, such as suboptimal electrode placement or reduced nerve survival. However, the psychophysical methods required to obtain these data are time intensive and may not be practical during a clinical mapping procedure, especially for young children. Here we have extended the previous investigation to determine if a physiological approach could provide a similar assessment of channel functionality. We hypothesized that, in accordance with the perceptual measures, higher EABR thresholds would correlate with steeper EABR amplitude growth functions, reflecting a degraded electrode-neuron interface. Design Data were collected from six cochlear implant listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the partial tripolar configuration, for which a fraction of current (σ) from a center active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. EABRs were obtained in each subject for the two channels having the highest and lowest tripolar (σ=1 or 0.9) behavioral threshold. Evoked potentials were measured with both the monopolar (σ=0) and a more focused partial tripolar (σ ≥ 0.50) configuration. Results Consistent with previous studies, EABR thresholds were highly and positively correlated with behavioral thresholds

  14. Identifying cochlear implant channels with poor electrode-neuron interfaces: electrically evoked auditory brain stem responses measured with the partial tripolar configuration.

    Science.gov (United States)

    Bierer, Julie Arenberg; Faulkner, Kathleen F; Tremblay, Kelly L

    2011-01-01

    The goal of this study was to compare cochlear implant behavioral measures and electrically evoked auditory brain stem responses (EABRs) obtained with a spatially focused electrode configuration. It has been shown previously that channels with high thresholds, when measured with the tripolar configuration, exhibit relatively broad psychophysical tuning curves. The elevated threshold and degraded spatial/spectral selectivity of such channels are consistent with a poor electrode-neuron interface, defined as suboptimal electrode placement or reduced nerve survival. However, the psychophysical methods required to obtain these data are time intensive and may not be practical during a clinical mapping session, especially for young children. Here, we have extended the previous investigation to determine whether a physiological approach could provide a similar assessment of channel functionality. We hypothesized that, in accordance with the perceptual measures, higher EABR thresholds would correlate with steeper EABR amplitude growth functions, reflecting a degraded electrode-neuron interface. Data were collected from six cochlear implant listeners implanted with the HiRes 90k cochlear implant (Advanced Bionics). Single-channel thresholds and most comfortable listening levels were obtained for stimuli that varied in presumed electrical field size by using the partial tripolar configuration, for which a fraction of current (σ) from a center active electrode returns through two neighboring electrodes and the remainder through a distant indifferent electrode. EABRs were obtained in each subject for the two channels having the highest and lowest tripolar (σ = 1 or 0.9) behavioral threshold. Evoked potentials were measured with both the monopolar (σ = 0) and a more focused partial tripolar (σ ≥ 0.50) configuration. Consistent with previous studies, EABR thresholds were highly and positively correlated with behavioral thresholds obtained with both the monopolar and partial

  15. Glucose concentrations modulate brain-derived neurotrophic factor responsiveness of neurones in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    McIsaac, W; Ferguson, A V

    2017-04-01

    The hypothalamic paraventricular nucleus (PVN) is critical for normal energy balance and has been shown to contain high levels of both brain-derived neurotrophic factor (BDNF) and tropomyosin-receptor kinase B mRNA. Microinjections of BDNF into the PVN increase energy expenditure, suggesting that BDNF plays an important role in energy homeostasis through direct actions in this nucleus. The present study aimed to examine the postsynaptic effects of BDNF on the membrane potential of PVN neurones, and also to determine whether extracellular glucose concentrations modulated these effects. We used hypothalamic PVN slices from male Sprague-Dawley rats to perform whole cell current-clamp recordings from PVN neurones. BDNF was bath applied at a concentration of 2 nmol L -1 and the effects on membrane potential determined. BDNF caused depolarisations in 54% of neurones (n=25; mean±SEM, 8.9±1.2 mV) and hyperpolarisations in 23% (n=11; -6.7±1.4 mV), whereas the remaining cells were unaffected. These effects were maintained in the presence of tetrodotoxin (n=9; 56% depolarised, 22% hyperpolarised, 22% nonresponders), or the GABA a antagonist bicuculline (n=12; 42% depolarised, 17% hyperpolarised, 41% nonresponders), supporting the conclusion that these effects on membrane potential were postsynaptic. Current-clamp recordings from PVN neurones next examined the effects of BDNF on these neurones at varying extracellular glucose concentrations. Larger proportions of PVN neurones hyperpolarised in response to BDNF as the glucose concentrations decreased [10 mmol L -1 glucose 23% (n=11) of neurones hyperpolarised, whereas, at 0.2 mmol L -1 glucose, 71% showed hyperpolarising effects (n=12)]. Our findings reveal that BDNF has direct GABA A independent effects on PVN neurones, which are modulated by local glucose concentrations. The latter observation further emphasises the critical importance of using physiologically relevant conditions in an investigation of the central

  16. Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus

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    Zesemdorj Otgon-Uul

    2016-08-01

    Full Text Available Objective: The dorsomedial hypothalamus (DMH has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY, cocaine- and amphetamine-regulated transcript (CART, cholecystokinin (CCK, leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. Methods: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. Results: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN, where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. Conclusion: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. Keywords: Dorsomedial hypothalamus, GABAergic neuron, Feeding, Leptin, Glucose, Optogenetics

  17. Molecular phenotyping of transient postnatal tyrosine hydroxylase neurons in the rat bed nucleus of the stria terminalis.

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    Carter, David A

    2017-07-01

    The bed nucleus of the stria terminalis (BNST) is a complex integrative centre in the forebrain, composed of multiple sub-nuclei, each with discrete populations of neurons. Progress in understanding BNST function, both in the adult and during postnatal maturation, is dependent upon a more complete characterization of neuronal phenotypes in the BNST. The aim of the current study was to define the molecular phenotype of one postnatal BNST neuronal population, in order to identify molecular factors that may underlie both (protein marker-related) immaturity, and secondly, the transience of this phenotype. This BNST population was originally identified by high, but transient expression of the EGR1 transcription factor (TF) in postnatal rat lateral intermediate BNST (BNSTLI). The current results confirm a high level of Egr1 activation in postnatal day 10 (PN10) male BNSTLI that is lost at PN40, and now demonstrate a similar pattern of transient activation in female brains. Apparent cellular immaturity in this population, as indicated by low levels of the adult neuronal marker NeuN/RBFOX3, was found to be uncorrelated with both key neuronal regulator protein expression (SOX2 and REST), and also RBFOX2 protein levels. The BNSTLI neurons have a partial catecholaminergic phenotype (tyrosine hydroxylase-positive/dopa decarboxylase-negative; TH+ve/DDC-ve) that is lost at PN40. In contrast, the co-expressed neuropeptide, somatostatin, is maintained, albeit at lower levels, at PN40. The transcriptional basis of the transient and partial catecholaminergic phenotype was investigated by analysing TFs known to maintain adult dopaminergic (TH+ve/DDC+ve) neuronal phenotypes. The BNSTLI neurons were shown to lack forkhead TFs including FOXA1, FOXA2 and FOXO1. In addition, the BNSTLI neurons had low, primarily cytoplasmic, expression of NR4A2/NURR1, an orphan nuclear receptor that is critical for adult maintenance of midbrain dopamine neurons. These results detail the molecular features

  18. Competitor suppresses neuronal representation of food reward in the nucleus accumbens/medial striatum of domestic chicks.

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    Amita, Hidetoshi; Matsushima, Toshiya

    2014-07-15

    To investigate the role of social contexts in controlling the neuronal representation of food reward, we recorded single neuron activity in the medial striatum/nucleus accumbens of domestic chicks and examined whether activities differed between two blocks with different contexts. Chicks were trained in an operant task to associate light-emitting diode color cues with three trial types that differed in the type of food reward: no reward (S-), a small reward/short-delay option (SS), and a large reward/long-delay alternative (LL). Amount and duration of reward were set such that both of SS and LL were chosen roughly equally. Neurons showing distinct cue-period activity in rewarding trials (SS and LL) were identified during an isolation block, and activity patterns were compared with those recorded from the same neuron during a subsequent pseudo-competition block in which another chick was allowed to forage in the same area, but was separated by a transparent window. In some neurons, cue-period activity was lower in the pseudo-competition block, and the difference was not ascribed to the number of repeated trials. Comparison at neuronal population level revealed statistically significant suppression in the pseudo-competition block in both SS and LL trials, suggesting that perceived competition generally suppressed the representation of cue-associated food reward. The delay- and reward-period activities, however, did not significantly different between blocks. These results demonstrate that visual perception of a competitive forager per se weakens the neuronal representation of predicted food reward. Possible functional links to impulse control are discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Nucleus accumbens core medium spiny neuron electrophysiological properties and partner preference behavior in the adult male prairie vole, Microtus ochrogaster.

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    Willett, Jaime A; Johnson, Ashlyn G; Vogel, Andrea R; Patisaul, Heather B; McGraw, Lisa A; Meitzen, John

    2018-04-01

    Medium spiny neurons (MSNs) in the nucleus accumbens have long been implicated in the neurobiological mechanisms that underlie numerous social and motivated behaviors as studied in rodents such as rats. Recently, the prairie vole has emerged as an important model animal for studying social behaviors, particularly regarding monogamy because of its ability to form pair bonds. However, to our knowledge, no study has assessed intrinsic vole MSN electrophysiological properties or tested how these properties vary with the strength of the pair bond between partnered voles. Here we performed whole cell patch-clamp recordings of MSNs in acute brain slices of the nucleus accumbens core (NAc) of adult male voles exhibiting strong and weak preferences for their respective partnered females. We first document vole MSN electrophysiological properties and provide comparison to rat MSNs. Vole MSNs demonstrated many canonical electrophysiological attributes shared across species but exhibited notable differences in excitability compared with rat MSNs. Second, we assessed male vole partner preference behavior and tested whether MSN electrophysiological properties varied with partner preference strength. Male vole partner preference showed extensive variability. We found that decreases in miniature excitatory postsynaptic current amplitude and the slope of the evoked action potential firing rate to depolarizing current injection weakly associated with increased preference for the partnered female. This suggests that excitatory synaptic strength and neuronal excitability may be decreased in MSNs in males exhibiting stronger preference for a partnered female. Overall, these data provide extensive documentation of MSN electrophysiological characteristics and their relationship to social behavior in the prairie vole. NEW & NOTEWORTHY This research represents the first assessment of prairie vole nucleus accumbens core medium spiny neuron intrinsic electrophysiological properties and

  20. Dynamic stereotypic responses of basal ganglia neurons to subthalamic nucleus high frequency stimulation in the parkinsonian primate

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    Anan eMoran

    2011-04-01

    Full Text Available Deep brain stimulation in the subthalamic nucleus (STN is a well-established therapy for patients with severe Parkinson‟s disease (PD; however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia during high frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, basal ganglia output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial

  1. Dynamic stereotypic responses of Basal Ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate.

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    Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

    2011-01-01

    Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD.

  2. Ovarian hormone deprivation reduces oxytocin expression in Paraventricular Nucleus preautonomic neurons and correlates with baroreflex impairment in rats

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    Vitor Ulisses De Melo

    2016-10-01

    Full Text Available The prevalence of cardiovascular diseases including hypertension increases dramatically in women after menopause, however the mechanisms involved remain incompletely understood. Oxytocinergic (OTergic neurons are largely present within the paraventricular nucleus of the hypothalamus (PVN. Several studies have shown that OTergic drive from PVN to brainstem increases baroreflex sensitivity and improves autonomic control of the circulation. Since preautonomic PVN neurons express different types of estrogen receptors, we hypothesize that ovarian hormone deprivation causes baroreflex impairment, autonomic imbalance and hypertension by negatively impacting OTergic drive and oxytocin levels in pre-autonomic neurons. Here, we assessed oxytocin gene and protein expression (qPCR and immunohistochemistry within PVN subnuclei in sham-operated and ovariectomized Wistar rats. Conscious hemodynamic recordings were used to assess resting blood pressure and heart rate and the autonomic modulation of heart and vessels was estimated by power spectral analysis. We observed that the ovarian hormone deprivation in ovariectomized rats decreased baroreflex sensitivity, increased sympathetic and reduced vagal outflows to the heart and augmented the resting blood pressure. Of note, ovariectomized rats had reduced PVN oxytocin mRNA and protein expression in all pre-autonomic PVN subnuclei. Furthermore, reduced PVN oxytocin protein levels were positively correlated with decreased baroreflex sensitivity and negatively correlated with increased LF/HF ratio. These findings suggest that reduced oxytocin expression in OTergic neurons of the PVN contributes to the baroreflex dysfunction and autonomic dysregulation observed with ovarian hormone deprivation.

  3. Morphine treatment enhances glutamatergic input onto neurons of the nucleus accumbens via both disinhibitory and stimulating effect.

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    Yuan, Kejing; Sheng, Huan; Song, Jiaojiao; Yang, Li; Cui, Dongyang; Ma, Qianqian; Zhang, Wen; Lai, Bin; Chen, Ming; Zheng, Ping

    2017-11-01

    Drug addiction is a chronic brain disorder characterized by the compulsive repeated use of drugs. The reinforcing effect of repeated use of drugs on reward plays an important role in morphine-induced addictive behaviors. The nucleus accumbens (NAc) is an important site where morphine treatment produces its reinforcing effect on reward. However, how morphine treatment produces its reinforcing effect on reward in the NAc remains to be clarified. In the present study, we studied the influence of morphine treatment on the effects of DA and observed whether morphine treatment could directly change glutamatergic synaptic transmission in the NAc. We also explored the functional significance of morphine-induced potentiation of glutamatergic synaptic transmission in the NAc at behavioral level. Our results show that (1) morphine treatment removes the inhibitory effect of DA on glutamatergic input onto NAc neurons; (2) morphine treatment potentiates glutamatergic input onto NAc neurons, especially the one from the basolateral amygdala (BLA) to the NAc; (3) blockade of glutamatergic synaptic transmission in the NAc or ablation of projection neurons from BLA to NAc significantly decreases morphine treatment-induced increase in locomotor activity. These results suggest that morphine treatment enhances glutamatergic input onto neurons of the NAc via both disinhibitory and stimulating effect and therefore increases locomotor activity. © 2016 Society for the Study of Addiction.

  4. High and low frequency stimulation of the subthalamic nucleus induce prolonged changes in subthalamic and globus pallidus neurons

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    Hagar eLavian

    2013-12-01

    Full Text Available High frequency stimulation (HFS of the subthalamic nucleus (STN is widely used to treat the symptoms of Parkinson’s disease but the mechanism of this therapy is unclear. Using a rat brain slice preparation maintaining the connectivity between the STN and one of its target nuclei, the globus pallidus (GP, we investigated the effects of high and low frequency stimulation (HFS 100 Hz, LFS 10 Hz on activity of single neurons in the STN and GP. Both HFS and LFS caused changes in firing frequency and pattern of subthalamic and pallidal neurons. These changes were of synaptic origin, as they were abolished by glutamate and GABA antagonists. Both HFS and LFS also induced a long-lasting reduction in firing frequency in STN neurons possibly contending a direct causal link between HFS and the outcome DBS. In the GP both HFS and LFS induced either a long-lasting depression, or less frequently, a long-lasting excitation. Thus, in addition to the intrinsic activation of the stimulated neurons, long-lasting stimulation of the STN may trigger prolonged biochemical processes.

  5. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala

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    Adams, Thomas; Rosenkranz, J Amiel

    2016-01-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders. PMID:26677945

  6. Social Isolation During Postweaning Development Causes Hypoactivity of Neurons in the Medial Nucleus of the Male Rat Amygdala.

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    Adams, Thomas; Rosenkranz, J Amiel

    2016-06-01

    Children exposed to neglect or social deprivation are at heightened risk for psychiatric disorders and abnormal social patterns as adults. There is also evidence that prepubertal neglect in children causes abnormal metabolic activity in several brain regions, including the amygdala area. The medial nucleus of the amygdala (MeA) is a key region for performance of social behaviors and still undergoes maturation during the periadolescent period. As such, the normal development of this region may be disrupted by social deprivation. In rodents, postweaning social isolation causes a range of deficits in sexual and agonistic behaviors that normally rely on the posterior MeA (MeAp). However, little is known about the effects of social isolation on the function of MeA neurons. In this study, we tested whether postweaning social isolation caused abnormal activity of MeA neurons. We found that postweaning social isolation caused a decrease of in vivo firing activity of MeAp neurons, and reduced drive from excitatory afferents. In vitro electrophysiological studies found that postweaning social isolation caused a presynaptic impairment of excitatory input to the dorsal MeAp, but a progressive postsynaptic reduction of membrane excitability in the ventral MeAp. These results demonstrate discrete, subnucleus-specific effects of social deprivation on the physiology of MeAp neurons. This pathophysiology may contribute to the disruption of social behavior after developmental social deprivation, and may be a novel target to facilitate the treatment of social disorders.

  7. Cervical vagus nerve stimulation augments spontaneous discharge in second- and higher-order sensory neurons in the rat nucleus of the solitary tract.

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    Beaumont, Eric; Campbell, Regenia P; Andresen, Michael C; Scofield, Stephanie; Singh, Krishna; Libbus, Imad; KenKnight, Bruce H; Snyder, Logan; Cantrell, Nathan

    2017-08-01

    Vagus nerve stimulation (VNS) currently treats patients with drug-resistant epilepsy, depression, and heart failure. The mild intensities used in chronic VNS suggest that primary visceral afferents and central nervous system activation are involved. Here, we measured the activity of neurons in the nucleus of the solitary tract (NTS) in anesthetized rats using clinically styled VNS. Our chief findings indicate that VNS at threshold bradycardic intensity activated NTS neuron discharge in one-third of NTS neurons. This VNS directly activated only myelinated vagal afferents projecting to second-order NTS neurons. Most VNS-induced activity in NTS, however, was unsynchronized to vagal stimuli. Thus, VNS activated unsynchronized activity in NTS neurons that were second order to vagal afferent C-fibers as well as higher-order NTS neurons only polysynaptically activated by the vagus. Overall, cardiovascular-sensitive and -insensitive NTS neurons were similarly activated by VNS: 3/4 neurons with monosynaptic vagal A-fiber afferents, 6/42 neurons with monosynaptic vagal C-fiber afferents, and 16/21 polysynaptic NTS neurons. Provocatively, vagal A-fibers indirectly activated C-fiber neurons during VNS. Elevated spontaneous spiking was quantitatively much higher than synchronized activity and extended well into the periods of nonstimulation. Surprisingly, many polysynaptic NTS neurons responded to half the bradycardic intensity used in clinical studies, indicating that a subset of myelinated vagal afferents is sufficient to evoke VNS indirect activation. Our study uncovered a myelinated vagal afferent drive that indirectly activates NTS neurons and thus central pathways beyond NTS and support reconsideration of brain contributions of vagal afferents underpinning of therapeutic impacts. NEW & NOTEWORTHY Acute vagus nerve stimulation elevated activity in neurons located in the medial nucleus of the solitary tract. Such stimuli directly activated only myelinated vagal afferents

  8. Enhanced astroglial GABA uptake attenuates tonic GABAA inhibition of the presympathetic hypothalamic paraventricular nucleus neurons in heart failure.

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    Pandit, Sudip; Jo, Ji Yoon; Lee, Sang Ung; Lee, Young Jae; Lee, So Yeong; Ryu, Pan Dong; Lee, Jung Un; Kim, Hyun-Woo; Jeon, Byeong Hwa; Park, Jin Bong

    2015-08-01

    γ-Aminobutyric acid (GABA) generates persistent tonic inhibitory currents (Itonic) and conventional inhibitory postsynaptic currents in the hypothalamic paraventricular nucleus (PVN) via activation of GABAA receptors (GABAARs). We investigated the pathophysiological significance of astroglial GABA uptake in the regulation of Itonic in the PVN neurons projecting to the rostral ventrolateral medulla (PVN-RVLM). The Itonic of PVN-RVLM neurons were significantly reduced in heart failure (HF) compared with sham-operated (SHAM) rats. Reduced Itonic sensitivity to THIP argued for the decreased function of GABAAR δ subunits in HF, whereas similar Itonic sensitivity to benzodiazepines argued against the difference of γ2 subunit-containing GABAARs in SHAM and HF rats. HF Itonic attenuation was reversed by a nonselective GABA transporter (GAT) blocker (nipecotic acid, NPA) and a GAT-3 selective blocker, but not by a GAT-1 blocker, suggesting that astroglial GABA clearance increased in HF. Similar and minimal Itonic responses to bestrophin-1 blockade in SHAM and HF neurons further argued against a role for astroglial GABA release in HF Itonic attenuation. Finally, the NPA-induced inhibition of spontaneous firing was greater in HF than in SHAM PVN-RVLM neurons, whereas diazepam induced less inhibition of spontaneous firing in HF than in SHAM neurons. Overall, our results showed that combined with reduced GABAARs function, the enhanced astroglial GABA uptake-induced attenuation of Itonic in HF PVN-RVLM neurons explains the deficit in tonic GABAergic inhibition and increased sympathetic outflow from the PVN during heart failure. Copyright © 2015 the American Physiological Society.

  9. Apolipoprotein A-IV inhibits AgRP/NPY neurons and activates POMC neurons in the arcuate nucleus

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    Apolipoprotein A-IV (apoA-IV) in the brain potently suppresses food intake. However the mechanisms underlying its anorexigenic effects remain to be identified. We first examined the effects of apoA-IV on cellular activities in hypothalamic neurons that co-express agouti-related peptide (AgRP) and ne...

  10. A rapid method combining Golgi and Nissl staining to study neuronal morphology and cytoarchitecture.

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    Pilati, Nadia; Barker, Matthew; Panteleimonitis, Sofoklis; Donga, Revers; Hamann, Martine

    2008-06-01

    The Golgi silver impregnation technique gives detailed information on neuronal morphology of the few neurons it labels, whereas the majority remain unstained. In contrast, the Nissl staining technique allows for consistent labeling of the whole neuronal population but gives very limited information on neuronal morphology. Most studies characterizing neuronal cell types in the context of their distribution within the tissue slice tend to use the Golgi silver impregnation technique for neuronal morphology followed by deimpregnation as a prerequisite for showing that neuron's histological location by subsequent Nissl staining. Here, we describe a rapid method combining Golgi silver impregnation with cresyl violet staining that provides a useful and simple approach to combining cellular morphology with cytoarchitecture without the need for deimpregnating the tissue. Our method allowed us to identify neurons of the facial nucleus and the supratrigeminal nucleus, as well as assessing cellular distribution within layers of the dorsal cochlear nucleus. With this method, we also have been able to directly compare morphological characteristics of neuronal somata at the dorsal cochlear nucleus when labeled with cresyl violet with those obtained with the Golgi method, and we found that cresyl violet-labeled cell bodies appear smaller at high cellular densities. Our observation suggests that cresyl violet staining is inadequate to quantify differences in soma sizes.

  11. Electrophysiological and morphological properties of neurons in the prepositus hypoglossi nucleus that express both ChAT and VGAT in a double-transgenic rat model.

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    Saito, Yasuhiko; Zhang, Yue; Yanagawa, Yuchio

    2015-04-01

    Although it has been proposed that neurons that contain both acetylcholine (ACh) and γ-aminobutyric acid (GABA) are present in the prepositus hypoglossi nucleus (PHN), these neurons have not been characterized because of the difficulty in identifying them. In the present study, PHN neurons that express both choline acetyltransferase and the vesicular GABA transporter (VGAT) were identified using double-transgenic rats, in which the cholinergic and inhibitory neurons express the fluorescent proteins tdTomato and Venus, respectively. To characterize the neurons that express both tdTomato and Venus (D+ neurons), the afterhyperpolarization (AHP) profiles and firing patterns of these neurons were investigated via whole-cell recordings of brainstem slice preparations. Regarding the three AHP profiles and four firing patterns that the D+ neurons exhibited, an AHP with an afterdepolarization and a firing pattern that exhibited a delay in the generation of the first spike were the preferential properties of these neurons. In the three morphological types classified, the multipolar type that exhibited radiating dendrites was predominant among the D+ neurons. Immunocytochemical analysis revealed that the VGAT-immunopositive axonal boutons that expressed tdTomato were primarily located in the dorsal cap of inferior olive (IO) and the PHN. Although the PHN receives cholinergic inputs from the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus, D+ neurons were absent from these brain areas. Together, these results suggest that PHN neurons that co-express ACh and GABA exhibit specific electrophysiological and morphological properties, and innervate the dorsal cap of the IO and the PHN. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  12. Reward and behavioral factors contributing to the tonic activity of monkey pedunculopontine tegmental nucleus neurons during saccade tasks

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    Ken-ichi Okada

    2016-11-01

    Full Text Available The pedunculopontine tegmental nucleus (PPTg in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target, then made saccades to the peripheral saccade target, and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity

  13. Reward and Behavioral Factors Contributing to the Tonic Activity of Monkey Pedunculopontine Tegmental Nucleus Neurons during Saccade Tasks.

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    Okada, Ken-Ichi; Kobayashi, Yasushi

    2016-01-01

    The pedunculopontine tegmental nucleus (PPTg) in the brainstem plays a role in controlling reinforcement learning and executing conditioned behavior. We previously examined the activity of PPTg neurons in monkeys during a reward-conditioned, visually guided saccade task, and reported that a population of these neurons exhibited tonic responses throughout the task period. These tonic responses might depend on prediction of the upcoming reward, successful execution of the task, or both. Here, we sought to further distinguish these factors and to investigate how each contributes to the tonic neuronal activity of the PPTg. In our normal visually guided saccade task, the monkey initially fixated on the central fixation target (FT), then made saccades to the peripheral saccade target and received a juice reward after the saccade target disappeared. Most of the tonic activity terminated shortly after the reward delivery, when the monkey broke fixation. To distinguish between reward and behavioral epochs, we then changed the task sequence for a block of trials, such that the saccade target remained visible after the reward delivery. Under these visible conditions, the monkeys tended to continue fixating on the saccade target even after the reward delivery. Therefore, the prediction of the upcoming reward and the end of an individual trial were separated in time. Regardless of the task conditions, half of the tonically active PPTg neurons terminated their activity around the time of the reward delivery, consistent with the view that PPTg neurons might send reward prediction signals until the time of reward delivery, which is essential for computing reward prediction error in reinforcement learning. On the other hand, the other half of the tonically active PPTg neurons changed their activity dependent on the task condition. In the normal condition, the tonic responses terminated around the time of the reward delivery, while in the visible condition, the activity continued

  14. The calcium-binding protein parvalbumin modulates the firing 1 properties of the reticular thalamic nucleus bursting neurons.

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    Albéri, Lavinia; Lintas, Alessandra; Kretz, Robert; Schwaller, Beat; Villa, Alessandro E P

    2013-06-01

    The reticular thalamic nucleus (RTN) of the mouse is characterized by an overwhelming majority of GABAergic neurons receiving afferences from both the thalamus and the cerebral cortex and sending projections mainly on thalamocortical neurons. The RTN neurons express high levels of the "slow Ca(2+) buffer" parvalbumin (PV) and are characterized by low-threshold Ca(2+) currents, I(T). We performed extracellular recordings in ketamine/xylazine anesthetized mice in the rostromedial portion of the RTN. In the RTN of wild-type and PV knockout (PVKO) mice we distinguished four types of neurons characterized on the basis of their firing pattern: irregular firing (type I), medium bursting (type II), long bursting (type III), and tonically firing (type IV). Compared with wild-type mice, we observed in the PVKOs the medium bursting (type II) more frequently than the long bursting type and longer interspike intervals within the burst without affecting the number of spikes. This suggests that PV may affect the firing properties of RTN neurons via a mechanism associated with the kinetics of burst discharges. Ca(v)3.2 channels, which mediate the I(T) currents, were more localized to the somatic plasma membrane of RTN neurons in PVKO mice, whereas Ca(v)3.3 expression was similar in both genotypes. The immunoelectron microscopy analysis showed that Ca(v)3.2 channels were localized at active axosomatic synapses, thus suggesting that the differential localization of Ca(v)3.2 in the PVKOs may affect bursting dynamics. Cross-correlation analysis of simultaneously recorded neurons from the same electrode tip showed that about one-third of the cell pairs tended to fire synchronously in both genotypes, independent of PV expression. In summary, PV deficiency does not affect the functional connectivity between RTN neurons but affects the distribution of Ca(v)3.2 channels and the dynamics of burst discharges of RTN cells, which in turn regulate the activity in the thalamocortical circuit.

  15. Neuronal Correlates of Fear Conditioning in the Bed Nucleus of the Stria Terminalis

    Science.gov (United States)

    Haufler, Darrell; Nagy, Frank Z.; Pare, Denis

    2013-01-01

    Lesion and inactivation studies indicate that the central amygdala (CeA) participates in the expression of cued and contextual fear, whereas the bed nucleus of the stria terminalis (BNST) is only involved in the latter. The basis for this functional dissociation is unclear because CeA and BNST form similar connections with the amygdala and…

  16. The Suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons

    NARCIS (Netherlands)

    Buijs, Ruud M.; la Fleur, Susanne E.; Wortel, Joke; van Heyningen, Caroline; Zuiddam, Laura; Mettenleiter, Thomas C.; Kalsbeek, Andries; Nagai, Katsuya; Niijima, Akira

    2003-01-01

    Opposing parasympathetic and sympathetic signals determine the autonomic output of the brain to the body and the change in balance over the sleep-wake cycle. The suprachiasmatic nucleus (SCN) organizes the activity/inactivity cycle and the behaviors that go along with it, but it is unclear how the

  17. Coding of information about tactile stimuli by neurones of the cuneate nucleus.

    Science.gov (United States)

    Douglas, P R; Ferrington, D G; Rowe, M

    1978-12-01

    1. The responses of cuneate neurones to controlled tactile stimulation of the foot pads were examined in unanaesthetized, decerebrate cats. The neurones were divided into three functional classes; one sensitive to steady tactile stimuli, and two dynamically sensitive classes which could be readily differentiated by their responsiveness to cutaneous vibration. Each class appeared to receive an exclusive input from only one of the three known groups of tactile receptors associated with the foot pads, namely the Pacinian corpuscles, the Merkel endings and the intradermal, encapsulated endings known as Krause or Meissner corpuscles. 2. Cuneate neurones responsive to steady indentation of the skin displayed approximately linear or sigmoidal stimulus-response relations over indentation ranges up to approximately 1.5--2 mm. Response variability at a fixed stimulus intensity was relatively low and showed little systematic change over the full range of the stimulus-response curves. 3. One class of dynamically sensitive cuneate neurones responded to cutaneous vibration over a range of approximately 5-80 Hz with maximal responsiveness around 30 Hz. The other class, the Pacinian neurones, responded over a range of approximately 80- greater than 600 Hz with maximal responsiveness at 200-400 Hz. The thresholds and combined band width of vibratory sensitivity of these populations were comparable with known subjective thresholds and range of cutaneous vibratory sensibility. 4. Responses of cuneate neurones were phase-locked to the vibratory stimulus suggesting that information about vibration frequency could be coded by the patterns of impulse activity. Quantitative measures indicated that maximal phase-locking occurred in responses to vibration frequencies of 10-50 Hz with a progressive decline at higher frequencies. Above 400 Hz, impulse activity occurred almost randomly throughout the vibratory stimulus cycle and therefore carried little further signal of vibratory frequency

  18. Role of neuronal activity in regulating the structure and function of auditory neurons

    International Nuclear Information System (INIS)

    Born, D.E.

    1986-01-01

    The role of afferent activity in maintaining neuronal structure and function was investigated in second order auditory neurons in nucleus magnocellularis (NM) of the chicken. The cochlea provides the major excitatory input to NM neurons via the eighth nerve. Removal of the cochlea causes dramatic changes in NM neurons. To determine if the elimination of neuronal activity is responsible for the changes in NM seen after cochlea removal, tetrodotoxin was used block action potentials in the cochlear ganglion cells. Tetrodotoxin injections into the perilymph reliably blocked neuronal activity in the cochlear nerve and NM. Far field recordings of sound-evoked potentials revealed that responses returned within 6 hours. Changes in amino acid incorporation in NM neurons were measured by giving intracardiac injections of 3 H-leucine and preparing tissue for autoradiographic demonstration of incorporated amino acid. Grain counts over individual neurons revealed that a single injection of tetrodotoxin produced a 40% decrease in grain density in ipsilateral NM neurons. It is concluded that neuronal activity plays an important contribution to the maintenance of the normal properties of NM neurons

  19. Strong, reliable and precise synaptic connections between thalamic relay cells and neurones of the nucleus reticularis in juvenile rats

    Science.gov (United States)

    Gentet, Luc J; Ulrich, Daniel

    2003-01-01

    The thalamic reticular nucleus (nRT) is composed entirely of GABAergic inhibitory neurones that receive input from pyramidal cortical neurones and excitatory relay cells of the ventrobasal complex of the thalamus (VB). It plays a major role in the synchrony of thalamic networks, yet the synaptic connections it receives from VB cells have never been fully physiologically characterised. Here, whole-cell current-clamp recordings were obtained from 22 synaptically connected VB-nRT cell pairs in slices of juvenile (P14–20) rats. At 34–36 °C, single presynaptic APs evoked unitary EPSPs in nRT cells with a peak amplitude of 7.4 ± 1.5 mV (mean ± s.e.m.) and a decay time constant of 15.1 ± 0.9 ms. Only four out of 22 pairs showed transmission failures at a mean rate of 6.8 ± 1.1 %. An NMDA receptor (NMDAR)-mediated component was significant at rest and subsequent EPSPs in a train were depressed. Only one out of 14 pairs tested was reciprocally connected; the observed IPSPs in the VB cell had a peak amplitude of 0.8 mV and were completely abolished in the presence of 10 μm bicuculline. Thus, synaptic connections from VB cells to nRT neurones are mainly ‘drivers’, while a small subset of cells form closed disynaptic loops. PMID:12563005

  20. Daily changes in synaptic innervation of VIP neurons in the rat suprachiasmatic nucleus: contribution of glutamatergic afferents.

    Science.gov (United States)

    Girardet, Clémence; Blanchard, Marie-Pierre; Ferracci, Géraldine; Lévêque, Christian; Moreno, Mathias; François-Bellan, Anne-Marie; Becquet, Denis; Bosler, Olivier

    2010-01-01

    The daily temporal organization of rhythmic functions in mammals, which requires synchronization of the circadian clock to the 24-h light-dark cycle, is believed to involve adjustments of the mutual phasing of the cellular oscillators that comprise the time-keeper within the suprachiasmatic nucleus of the hypothalamus (SCN). Following from a previous study showing that the SCN undergoes day/night rearrangements of its neuronal-glial network that may be crucial for intercellular phasing, we investigated the contribution of glutamatergic synapses, known to play major roles in SCN functioning, to such rhythmic plastic events. Neither expression levels of the vesicular glutamate transporters nor numbers of glutamatergic terminals showed nycthemeral variations in the SCN. However, using quantitative imaging after combined immunolabelling, the density of synapses on neurons expressing vasoactive intestinal peptide, known as targets of the retinal input, increased during the day and both glutamatergic and non-glutamatergic synapses contributed to the increase (+36%). This was not the case for synapses made on vasopressin-containing neurons, the other major source of SCN efferents in the non-retinorecipient region. Together with electron microscope observations showing no differences in the morphometric features of glutamatergic terminals during the day and night, these data show that the light synchronization process in the SCN involves a selective remodelling of synapses at sites of photic integration. They provide a further illustration of how the adult brain may rapidly and reversibly adapt its synaptic architecture to functional needs.

  1. Gastrointestinal-projecting neurones in the dorsal motor nucleus of the vagus exhibit direct and viscerotopically organized sensitivity to orexin

    Science.gov (United States)

    Grabauskas, Gintautas; Moises, Hylan C

    2003-01-01

    Orexin (hypocretin)-containing projections from lateral hypothalamus (LH) are thought to play an important role in the regulation of feeding behaviour and energy balance. In rodent studies, central administration of orexin peptides increases food intake, and orexin neurones in the LH are activated by hypoglycaemia during fasting. In addition, administration of orexins into the fourth ventricle or the dorsal motor nucleus of the vagus (DMV) has been shown to stimulate gastric acid secretion and motility, respectively, via vagal efferent pathways. In this study, whole-cell recordings were obtained from DMV neurones in rat brainstem slices to investigate the cellular mechanism(s) by which orexins produce their gastrostimulatory effects. To determine whether responsiveness to orexins might be differentially expressed among distinct populations of preganglionic vagal motor neurones, recordings were made from neurones whose projections to the gastrointestinal tract had been identified by retrograde labelling following apposition of the fluorescent tracer DiI to the gastric fundus, corpus or antrum/pylorus, the duodenum or caecum. Additionally, the responses of neurones to orexins were compared with those produced by oxytocin, which acts within the DMV to stimulate gastric acid secretion, but inhibits gastric motor function. Bath application of orexin-A or orexin-B (30–300 nm) produced a slow depolarization, accompanied by increased firing in 47 of 102 DMV neurones tested, including 70 % (30/43) of those that projected to the gastric fundus or corpus. In contrast, few DMV neurones that supplied the antrum/pylorus (3/13), duodenum (4/18) or caecum (1/13) were responsive to these peptides. The depolarizing responses were concentration dependent and persisted during synaptic isolation of neurones with TTX or Cd2+, indicating they resulted from activation of postsynaptic orexin receptors. They were also associated with a small increase in membrane resistance, and in voltage

  2. Nutritional Programming of Accelerated Puberty in Heifers: Involvement of Pro-Opiomelanocortin Neurones in the Arcuate Nucleus.

    Science.gov (United States)

    Cardoso, R C; Alves, B R C; Sharpton, S M; Williams, G L; Amstalden, M

    2015-08-01

    The timing of puberty and subsequent fertility in female mammals are dependent on the integration of metabolic signals by the hypothalamus. Pro-opiomelanocortin (POMC) neurones in the arcuate nucleus (ARC) comprise a critical metabolic-sensing pathway controlling the reproductive neuroendocrine axis. α-Melanocyte-stimulating hormone (αMSH), a product of the POMC gene, has excitatory effects on gonadotrophin-releasing hormone (GnRH) neurones and fibres containing αMSH project to GnRH and kisspeptin neurones. Because kisspeptin is a potent stimulator of GnRH release, αMSH may also stimulate GnRH secretion indirectly via kisspeptin neurones. In the present work, we report studies conducted in young female cattle (heifers) aiming to determine whether increased nutrient intake during the juvenile period (4-8 months of age), a strategy previously shown to advance puberty, alters POMC and KISS1 mRNA expression, as well as αMSH close contacts on GnRH and kisspeptin neurones. In Experiment 1, POMC mRNA expression, detected by in situ hybridisation, was greater (P high-gain, HG; n = 6) compared to heifers that gained 0.5 kg/day (low-gain, LG; n = 5). The number of KISS1-expressing cells in the middle ARC was reduced (P < 0.05) in HG compared to LG heifers. In Experiment 2, double-immunofluorescence showed limited αMSH-positive close contacts on GnRH neurones, and the magnitude of these inputs was not influenced by nutritional status. Conversely, a large number of kisspeptin-immunoreactive cells in the ARC were observed in close proximity to αMSH-containing varicosities. Furthermore, HG heifers (n = 5) exhibited a greater (P < 0.05) percentage of kisspeptin neurones in direct apposition to αMSH fibres and an increased (P < 0.05) number of αMSH close contacts per kisspeptin cell compared to LG heifers (n = 6). These results indicate that the POMC-kisspeptin pathway may be important in mediating the nutritional acceleration of puberty in heifers.

  3. H2O2 augments cytosolic calcium in nucleus tractus solitarii neurons via multiple voltage-gated calcium channels.

    Science.gov (United States)

    Ostrowski, Tim D; Dantzler, Heather A; Polo-Parada, Luis; Kline, David D

    2017-05-01

    Reactive oxygen species (ROS) play a profound role in cardiorespiratory function under normal physiological conditions and disease states. ROS can influence neuronal activity by altering various ion channels and transporters. Within the nucleus tractus solitarii (nTS), a vital brainstem area for cardiorespiratory control, hydrogen peroxide (H 2 O 2 ) induces sustained hyperexcitability following an initial depression of neuronal activity. The mechanism(s) associated with the delayed hyperexcitability are unknown. Here we evaluate the effect(s) of H 2 O 2 on cytosolic Ca 2+ (via fura-2 imaging) and voltage-dependent calcium currents in dissociated rat nTS neurons. H 2 O 2 perfusion (200 µM; 1 min) induced a delayed, slow, and moderate increase (~27%) in intracellular Ca 2+ concentration ([Ca 2+ ] i ). The H 2 O 2 -mediated increase in [Ca 2+ ] i prevailed during thapsigargin, excluding the endoplasmic reticulum as a Ca 2+ source. The effect, however, was abolished by removal of extracellular Ca 2+ or the addition of cadmium to the bath solution, suggesting voltage-gated Ca 2+ channels (VGCCs) as targets for H 2 O 2 modulation. Recording of the total voltage-dependent Ca 2+ current confirmed H 2 O 2 enhanced Ca 2+ entry. Blocking VGCC L, N, and P/Q subtypes decreased the number of cells and their calcium currents that respond to H 2 O 2 The number of responder cells to H 2 O 2 also decreased in the presence of dithiothreitol, suggesting the actions of H 2 O 2 were dependent on sulfhydryl oxidation. In summary, here, we have shown that H 2 O 2 increases [Ca 2+ ] i and its Ca 2+ currents, which is dependent on multiple VGCCs likely by oxidation of sulfhydryl groups. These processes presumably contribute to the previously observed delayed hyperexcitability of nTS neurons in in vitro brainstem slices. Copyright © 2017 the American Physiological Society.

  4. Intracellular Na(+) and metabolic modulation of Na/K pump and excitability in the rat suprachiasmatic nucleus neurons.

    Science.gov (United States)

    Wang, Yi-Chi; Yang, Jyh-Jeen; Huang, Rong-Chi

    2012-10-01

    Na/K pump activity and metabolic rate are both higher during the day in the suprachiasmatic nucleus (SCN) that houses the circadian clock. Here we investigated the role of intracellular Na(+) and energy metabolism in regulating Na/K pump activity and neuronal excitability. Removal of extracellular K(+) to block the Na/K pump excited SCN neurons to fire at higher rates and return to normal K(+) to reactivate the pump produced rebound hyperpolarization to inhibit firing. In the presence of tetrodotoxin to block the action potentials, both zero K(+)-induced depolarization and rebound hyperpolarization were blocked by the cardiac glycoside strophanthidin. Ratiometric Na(+) imaging with a Na(+)-sensitive fluorescent dye indicated saturating accumulation of intracellular Na(+) in response to pump blockade with zero K(+). The Na(+) ionophore monensin also induced Na(+) loading and hyperpolarized the membrane potential, with the hyperpolarizing effect of monensin abolished in zero Na(+) or by pump blockade. Conversely, Na(+) depletion with Na(+)-free pipette solution depolarized membrane potential but retained residual Na/K pump activity. Cyanide inhibition of oxidative phosphorylation blocked the Na/K pump to depolarize resting potential and increase spontaneous firing in most cells, and to raise intracellular Na(+) levels in all cells. Nonetheless, the Na/K pump was incompletely blocked by cyanide but completely blocked by iodoacetate to inhibit glycolysis, indicating the involvement of both oxidative phosphorylation and glycolysis in fueling the Na/K pump. Together, the results indicate the importance of intracellular Na(+) and energy metabolism in regulating Na/K pump activity as well as neuronal excitability in the SCN neurons.

  5. Effects of harmane (1-methyl-beta-carboline) on neurons in the nucleus accumbens of the rat.

    Science.gov (United States)

    Ergene, E; Schoener, E P

    1993-04-01

    Harmane, a beta-carboline alkaloid reported to exert locomotor and psychoactive effects, is found in certain plants and also has been shown to exist in the mammalian brain as an endogenous substance. In this study, the effects of locally perfused harmane were examined on spontaneous neuronal activity in the nucleus accumbens of urethane-anesthetized rats. Extracellular single-unit recording, coupled with push-pull perfusion, enabled the discrimination of specific, dose-related effects of harmane across a wide concentration range. At lower concentrations (10(-9)-10(-11) M), excitation prevailed, while at higher concentrations (10(-8)-10(-6) M) depression was most pronounced. These findings suggest a neuromodulatory role for harmane in the forebrain reward system.

  6. In situ hybridization of nucleus basalis neurons shows increased β-amyloid mRNA in Alzheimer disease

    International Nuclear Information System (INIS)

    Cohen, M.L.; Golde, T.E.; Usiak, M.F.; Younkin, L.H.; Younkin, S.G.

    1988-01-01

    To determine which cells within the brain produce β-amyloid mRNA and to assess expression of the β-amyloid gene in Alzheimer disease, the authors analyzed brain tissue from Alzheimer and control patients by in situ hybridization. The results demonstrate that β-amyloid mRNA is produced by neurons in the nucleus basalis of Meynert and cerebral cortex and that nuclues basalis perikarya from Alzheimer patients consistently hybridize more β-amyloid probe than those from controls. These observations support the hypothesis that increased expression of the β-amyloid gene plays an important role in the deposition of amyloid in the brains of patients with Alzheimer disease

  7. Neuronal degeneration induced by status epilepticus in the nucleus accumens of immature rats

    Czech Academy of Sciences Publication Activity Database

    Druga, Rastislav; Mareš, Pavel; Kubová, Hana

    2007-01-01

    Roč. 48, s6 (2007), s. 19-20 ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society. 31.112007-3.12.2007, Philadelphia] R&D Projects: GA ČR GA304/07/1137 Institutional research plan: CEZ:AV0Z50110509 Keywords : cpo1 * neuronal degeneration * status epilepticus * immature rat Subject RIV: FH - Neurology

  8. CRF1 receptor activation increases the response of neurons in the basolateral nucleus of the amygdala to afferent stimulation

    Directory of Open Access Journals (Sweden)

    2008-07-01

    Full Text Available The basolateral nucleus (BLA of the amygdala contributes to the consolidation of memories for emotional or stressful events. The nucleus contains a high density of CRF1 receptors that are activated by corticotropin-releasing factor (CRF. Modulation of the excitability of neurons in the BLA by CRF may regulate the immediate response to stressful events and the formation of associated memories. In the present study, CRF was found to increase the amplitude of field potentials recorded in the BLA following excitatory afferent stimulation, in vitro. The increase was mediated by CRF1 receptors, since it could be blocked by the selective, non-peptide antagonists, NBI30775 and NBI35583, but not by the CRF2-selective antagonist, astressin 2B. Furthermore, the CRF2-selective agonist, urocortin II had no effect on field potential amplitude. The increase induced by CRF was long-lasting, could not be reversed by subsequent administration of NBI35583, and required the activation of protein kinase C. This effect of CRF in the BLA may be important for increasing the salience of aversive stimuli under stressful conditions, and for enhancing the consolidation of associated memories. The results provide further justification for studying the efficacy of selective antagonists of the CRF1 receptor to reduce memory formation linked to emotional or traumatic events, and suggest that these compounds might be useful as prophylactic treatment for stress-related illness such as post-traumatic stress disorder.

  9. Lowering glucose level elevates [Ca2+]i in hypothalamic arcuate nucleus NPY neurons through P/Q-type Ca2+ channel activation and GSK3β inhibition

    Science.gov (United States)

    Chen, Yu; Zhou, Jun; Xie, Na; Huang, Chao; Zhang, Jun-qi; Hu, Zhuang-li; Ni, Lan; Jin, You; Wang, Fang; Chen, Jian-guo; Long, Li-hong

    2012-01-01

    Aim: To identify the mechanisms underlying the elevation of intracellular Ca2+ level ([Ca2+]i) induced by lowering extracellular glucose in rat hypothalamic arcuate nucleus NPY neurons. Methods: Primary cultures of hypothalamic arcuate nucleus (ARC) neurons were prepared from Sprague-Dawley rats. NPY neurons were identified with immunocytochemical method. [Ca2+]i was measured using fura-2 AM. Ca2+ current was recorded using whole-cell patch clamp recording. AMPK and GSK3β levels were measured using Western blot assay. Results: Lowering glucose level in the medium (from 10 to 1 mmol/L) induced a transient elevation of [Ca2+]i in ARC neurons, but not in hippocampal and cortical neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons depended on extracellular Ca2+, and was blocked by P/Q-type Ca2+channel blocker ω-agatoxin TK (100 nmol/L), but not by L-type Ca2+ channel blocker nifedipine (10 μmol/L) or N-type Ca2+channel blocker ω-conotoxin GVIA (300 nmol/L). Lowering glucose level increased the peak amplitude of high voltage-activated Ca2+ current in ARC neurons. The low-glucose induced elevation of [Ca2+]i in ARC neurons was blocked by the AMPK inhibitor compound C (20 μmol/L), and enhanced by the GSK3β inhibitor LiCl (10 mmol/L). Moreover, lowering glucose level induced the phosphorylation of AMPK and GSK3β, which was inhibited by compound C (20 μmol/L). Conclusion: Lowering glucose level enhances the activity of P/Q type Ca2+channels and elevates [Ca2+]i level in hypothalamic arcuate nucleus neurons via inhibition of GSK3β. PMID:22504905

  10. Hypocretin-1 (orexin A) prevents the effects of hypoxia/hypercapnia and enhances the GABAergic pathway from the lateral paragigantocellular nucleus to cardiac vagal neurons in the nucleus ambiguus.

    Science.gov (United States)

    Dergacheva, O; Philbin, K; Bateman, R; Mendelowitz, D

    2011-02-23

    Hypocretins (orexins) are hypothalamic neuropeptides that play a crucial role in regulating sleep/wake states and autonomic functions including parasympathetic cardiac activity. We have recently demonstrated stimulation of the lateral paragigantocellular nucleus (LPGi), the nucleus which is thought to play a role in rapid eye movement (REM) sleep control, activates an inhibitory pathway to preganglionic cardiac vagal neurons in the nucleus ambiguus (NA). In this study we test the hypothesis that hypocretin-1 modulates the inhibitory neurotransmission to cardiac vagal neurons evoked by stimulation of the LPGi using whole-cell patch-clamp recordings in an in vitro brain slice preparation from rats. Activation of hypocretin-1 receptors produced a dose-dependent and long-term facilitation of GABAergic postsynaptic currents evoked by electrical stimulation of the LPGi. Hypoxia/hypercapnia diminished LPGi-evoked GABAergic current in cardiac vagal neurons and this inhibition by hypoxia/hypercapnia was prevented by pre-application of hypocretin-1. The action of hypocretin-1 was blocked by the hypocretin-1 receptor antagonist SB-334867. Facilitation of LPGi-evoked GABAergic current in cardiac vagal neurons under both normal condition and during hypoxia/hypercapnia could be the mechanism by which hypocretin-1 affects parasympathetic cardiac function and heart rate during REM sleep. Furthermore, our findings indicate a new potential mechanism that might be involved in the cardiac arrhythmias, bradycardia, and sudden cardiac death that can occur during sleep. Copyright © 2011. Published by Elsevier Ltd.

  11. Exposure to an open-field arena increases c-Fos expression in a subpopulation of neurons in the dorsal raphe nucleus, including neurons projecting to the basolateral amygdaloid complex

    DEFF Research Database (Denmark)

    Hale, M.W.; Hay-Schmidt, A.; Mikkelsen, J.D.

    2008-01-01

    Serotonergic systems in the dorsal raphe nucleus are thought to play an important role in the regulation of anxiety states. To investigate responses of neurons in the dorsal raphe nucleus to a mild anxiety-related stimulus, we exposed rats to an open-field, under low-light or high-light conditions....... Treatment effects on c-Fos expression in serotonergic and non-serotonergic cells in the midbrain raphe nuclei were determined 2 h following open-field exposure or home cage control (CO) conditions. Rats tested under both light conditions responded with increases in c-Fos expression in serotonergic neurons...... within subdivisions of the midbrain raphe nuclei compared with CO rats. However, the total numbers of serotonergic neurons involved were small suggesting that exposure to the open-field may affect a subpopulation of serotonergic neurons. To determine if exposure to the open-field activates a subset...

  12. Biophysical properties and computational modeling of calcium spikes in serotonergic neurons of the dorsal raphe nucleus.

    Science.gov (United States)

    Tuckwell, Henry C

    2013-06-01

    Serotonergic neurons of the dorsal raphe nuclei, with their extensive innervation of nearly the whole brain have important modulatory effects on many cognitive and physiological processes. They play important roles in clinical depression and other psychiatric disorders. In order to quantify the effects of serotonergic transmission on target cells it is desirable to construct computational models and to this end these it is necessary to have details of the biophysical and spike properties of the serotonergic neurons. Here several basic properties are reviewed with data from several studies since the 1960s to the present. The quantities included are input resistance, resting membrane potential, membrane time constant, firing rate, spike duration, spike and afterhyperpolarization (AHP) amplitude, spike threshold, cell capacitance, soma and somadendritic areas. The action potentials of these cells are normally triggered by a combination of sodium and calcium currents which may result in autonomous pacemaker activity. We here analyse the mechanisms of high-threshold calcium spikes which have been demonstrated in these cells the presence of TTX (tetrodotoxin). The parameters for calcium dynamics required to give calcium spikes are quite different from those for regular spiking which suggests the involvement of restricted parts of the soma-dendritic surface as has been found, for example, in hippocampal neurons. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism.

    Science.gov (United States)

    Varin, Christophe; Rancillac, Armelle; Geoffroy, Hélène; Arthaud, Sébastien; Fort, Patrice; Gallopin, Thierry

    2015-07-08

    Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c-Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep-promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation. Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the

  14. Lead intoxication induces noradrenaline depletion, motor nonmotor disabilities, and changes in the firing pattern of subthalamic nucleus neurons.

    Science.gov (United States)

    Sabbar, M; Delaville, C; De Deurwaerdère, P; Benazzouz, A; Lakhdar-Ghazal, N

    2012-05-17

    Lead intoxication has been suggested as a high risk factor for the development of Parkinson disease. However, its impact on motor and nonmotor functions and the mechanism by which it can be involved in the disease are still unclear. In the present study, we studied the effects of lead intoxication on the following: (1) locomotor activity using an open field actimeter and motor coordination using the rotarod test, (2) anxiety behavior using the elevated plus maze, (3) "depression-like" behavior using sucrose preference test, and (4) subthalamic nucleus (STN) neuronal activity using extracellular single unit recordings. Male Sprague-Dawley rats were treated once a day with lead acetate or sodium acetate (20 mg/kg/d i.p.) during 3 weeks. The tissue content of monoamines was used to determine alteration of these systems at the end of experiments. Results show that lead significantly reduced exploratory activity, locomotor activity and the time spent on the rotarod bar. Furthermore, lead induced anxiety but not "depressive-like" behavior. The electrophysiological results show that lead altered the discharge pattern of STN neurons with an increase in the number of bursting and irregular cells without affecting the firing rate. Moreover, lead intoxication resulted in a decrease of tissue noradrenaline content without any change in the levels of dopamine and serotonin. Together, these results show for the first time that lead intoxication resulted in motor and nonmotor behavioral changes paralleled by noradrenaline depletion and changes in the firing activity of STN neurons, providing evidence consistent with the induction of atypical parkinsonian-like deficits. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  15. Cell Biological Mechanisms of Activity-Dependent Synapse to Nucleus Translocation of CRTC1 in Neurons

    Directory of Open Access Journals (Sweden)

    Toh Hean eCh'ng

    2015-09-01

    Full Text Available Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1 in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of synaptic glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation.

  16. Neurokinin B-producing projection neurons in the lateral stripe of the striatum and cell clusters of the accumbens nucleus in the rat.

    Science.gov (United States)

    Zhou, Ligang; Furuta, Takahiro; Kaneko, Takeshi

    2004-12-06

    Neurons producing preprotachykinin B (PPTB), the precursor of neurokinin B, constitute 5% of neurons in the dorsal striatum and project to the substantia innominata (SI) selectively. In the ventral striatum, PPTB-producing neurons are collected mainly in the lateral stripe of the striatum (LSS) and cell clusters of the accumbens nucleus (Acb). In the present study, we first examined the distribution of PPTB-immunoreactive neurons in rat ventral striatum and found that a large part of the PPTB-immunoreactive cell clusters was continuous to the LSS, but a smaller part was not. Thus, we divided the PPTB-immunoreactive cell clusters into the LSS-associated and non-LSS-associated ones. We next investigated the projection targets of the PPTB-producing ventral striatal neurons by combining immunofluorescence labeling and retrograde tracing. After injection of Fluoro-Gold into the basal component of the SI (SIb) and medial part of the interstitial nucleus of posterior limb of the anterior commissure, many PPTB-immunoreactive neurons were retrogradely labeled in the LSS-associated cell clusters and LSS, respectively. When the injection site included the ventral part of the sublenticular component of the SI(SIsl), retrogradely labeled neurons showed PPTB-immunoreactivity frequently in non-LSS-associated cell clusters. Furthermore, these PPTB-immunoreactive projections were confirmed by the double-fluorescence method after anterograde tracer injection into the ventral striatum containing the cell clusters. Since the dorsalmost part of the SIsl is known to receive strong inputs from PPTB-producing dorsal striatal neurons, the present results indicate that PPTB-producing ventral striatal neurons project to basal forebrain target regions in parallel with dorsal striatal neurons without significant convergence. 2004 Wiley-Liss, Inc.

  17. Neurons show the path: tip-to-nucleus communication in filamentous fungal development and pathogenesis.

    Science.gov (United States)

    Etxebeste, Oier; Espeso, Eduardo A

    2016-09-01

    Multiple fungal species penetrate substrates and accomplish host invasion through the fast, permanent and unidirectional extension of filamentous cells known as hyphae. Polar growth of hyphae results, however, in a significant increase in the distance between the polarity site, which also receives the earliest information about ambient conditions, and nuclei, where adaptive responses are executed. Recent studies demonstrate that these long distances are overcome by signal transduction pathways which convey sensory information from the polarity site to nuclei, controlling development and pathogenesis. The present review compares the striking connections of the mechanisms for long-distance communication in hyphae with those from neurons, and discusses the importance of their study in order to understand invasion and dissemination processes of filamentous fungi, and design strategies for developmental control in the future. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  18. Parkinsonian rest tremor can be detected accurately based on neuronal oscillations recorded from the subthalamic nucleus.

    Science.gov (United States)

    Hirschmann, J; Schoffelen, J M; Schnitzler, A; van Gerven, M A J

    2017-10-01

    To investigate the possibility of tremor detection based on deep brain activity. We re-analyzed recordings of local field potentials (LFPs) from the subthalamic nucleus in 10 PD patients (12 body sides) with spontaneously fluctuating rest tremor. Power in several frequency bands was estimated and used as input to Hidden Markov Models (HMMs) which classified short data segments as either tremor-free rest or rest tremor. HMMs were compared to direct threshold application to individual power features. Applying a threshold directly to band-limited power was insufficient for tremor detection (mean area under the curve [AUC] of receiver operating characteristic: 0.64, STD: 0.19). Multi-feature HMMs, in contrast, allowed for accurate detection (mean AUC: 0.82, STD: 0.15), using four power features obtained from a single contact pair. Within-patient training yielded better accuracy than across-patient training (0.84vs. 0.78, p=0.03), yet tremor could often be detected accurately with either approach. High frequency oscillations (>200Hz) were the best performing individual feature. LFP-based markers of tremor are robust enough to allow for accurate tremor detection in short data segments, provided that appropriate statistical models are used. LFP-based markers of tremor could be useful control signals for closed-loop deep brain stimulation. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  19. The effects of acute morphine treatment on the incorporation of [3H]L-lysine by normal and regenerating facial nucleus neurons

    International Nuclear Information System (INIS)

    Sinatra, R.S.; Ford, D.H.; Rhines, R.K.

    1979-01-01

    The effect of morphine on the incorporation of [ 3 H]L-lysine into proteins of facial nucleus neurons was examined by light microscopic radioautography. Silver grains present within various compartments of normal and regenerating (3-, 7-. 14- and 21 days post-axotomy) neurons from saline-treated Wistar rats were compared with the amount present in similar cells from animals receiving 40 mg/kg morphine sulfate i.v. At 14- and 21-days post-axotomy, regenerating neurons were larger and the grain count in the emulsion over these cells was greater than that observed in normal (unoperated) neurons. In normal facial neurons, the accumulation of lysine into the nucleus and nucleolus was significantly lower 60 min after morphine adminstration. However, morphine's inhibition of lysine incorporation was even more pronounced in regenerating neurons. In these cells, nuclear lysine uptake was depressed at 3 and 7 days, while maximum inhibition of cytoplasmic incorporation occurred at 14-days post-axotomy. Morphine adminstration decreased nucleolar lysine incorporation at all survival intervals. (Auth.)

  20. A population of kisspeptin/neurokinin B neurons in the arcuate nucleus may be the central target of the male effect phenomenon in goats.

    Science.gov (United States)

    Sakamoto, Kohei; Wakabayashi, Yoshihiro; Yamamura, Takashi; Tanaka, Tomomi; Takeuchi, Yukari; Mori, Yuji; Okamura, Hiroaki

    2013-01-01

    Exposure of females to a male pheromone accelerates pulsatile gonadotropin-releasing hormone (GnRH) secretion in goats. Recent evidence has suggested that neurons in the arcuate nucleus (ARC) containing kisspeptin and neurokinin B (NKB) play a pivotal role in the control of GnRH secretion. Therefore, we hypothesized that these neurons may be the central target of the male pheromone. To test this hypothesis, we examined whether NKB signaling is involved in the pheromone action, and whether ARC kisspeptin/NKB neurons receive input from the medial nucleus of the amygdala (MeA)--the nucleus suggested to relay pheromone signals. Ovariectomized goats were implanted with a recording electrode aimed at a population of ARC kisspeptin/NKB neurons, and GnRH pulse generator activity, represented by characteristic increases in multiple-unit activity (MUA) volleys, was measured. Pheromone exposure induced an MUA volley and luteinizing hormone (LH) pulse in control animals, whereas the MUA and LH responses to the pheromone were completely suppressed by the treatment with an NKB receptor antagonist. These results indicate that NKB signaling is a prerequisite for pheromone action. In ovariectomized goats, an anterograde tracer was injected into the MeA, and possible connections between the MeA and ARC kisspeptin/NKB neurons were examined. Histochemical observations demonstrated that a subset of ARC kisspeptin/NKB neurons receive efferent projections from the MeA. These results suggest that the male pheromone signal is conveyed via the MeA to ARC kisspeptin neurons, wherein the signal stimulates GnRH pulse generator activity through an NKB signaling-mediated mechanism in goats.

  1. Distinct roles of presynaptic dopamine receptors in the differential modulation of the intrinsic synapses of medium-spiny neurons in the nucleus accumbens

    Directory of Open Access Journals (Sweden)

    Schmauss Claudia

    2007-01-01

    Full Text Available Abstract Background In both schizophrenia and addiction, pathological changes in dopamine release appear to induce alterations in the circuitry of the nucleus accumbens that affect coordinated thought and motivation. Dopamine acts principally on medium-spiny GABA neurons, which comprise 95% of accumbens neurons and give rise to the majority of inhibitory synapses in the nucleus. To examine dopamine action at single medium-spiny neuron synapses, we imaged Ca2+ levels in their presynaptic varicosities in the acute brain slice using two-photon microscopy. Results Presynaptic Ca2+ rises were differentially modulated by dopamine. The D1/D5 selective agonist SKF81297 was exclusively facilitatory. The D2/D3 selective agonist quinpirole was predominantly inhibitory, but in some instances it was facilitatory. Studies using D2 and D3 receptor knockout mice revealed that quinpirole inhibition was either D2 or D3 receptor-mediated, while facilitation was mainly D3 receptor-mediated. Subsets of varicosities responded to both D1 and D2 agonists, showing that there was significant co-expression of these receptor families in single medium-spiny neurons. Neighboring presynaptic varicosities showed strikingly heterogeneous responses to DA agonists, suggesting that DA receptors may be differentially trafficked to individual varicosities on the same medium-spiny neuron axon. Conclusion Dopamine receptors are present on the presynaptic varicosities of medium-spiny neurons, where they potently control GABAergic synaptic transmission. While there is significant coexpression of D1 and D2 family dopamine receptors in individual neurons, at the subcellular level, these receptors appear to be heterogeneously distributed, potentially explaining the considerable controversy regarding dopamine action in the striatum, and in particular the degree of dopamine receptor segregation on these neurons. Assuming that post-receptor signaling is restricted to the microdomains of

  2. [A study on toxic effects of sodium salicylate on rat cochlear spiral ganglion neurons: dopamine receptors mediate expressions of NMDA and GABAA receptors].

    Science.gov (United States)

    Wei, Ting-Jia; Chen, Hui-Ying; Huang, Xi; Weng, Jing-Jin; Qin, Jiang-Yuan; Su, Ji-Ping

    2017-06-25

    The aim of the present study was to observe whether dopamine receptor (DR) was involved in the effects of sodium salicylate (SS) on the expressions of N-methyl-D-aspartic acid (NMDA) and γ-aminobutyric acid (GABA) receptors in rat cochlear spiral ganglion neurons (SGNs). Forty-eight hours after primary culture of rat SGNs, immunofluorescence technique was applied to detect expressions of DR1 and DR2, the two subtypes of dopamine receptors. Western blot was performed to assess NMDA receptor NR1 subunit and GABA A receptor subunit α2 (GABRα2) protein expressions in the SGNs after the treatments of SS alone or in combination with DR antagonists. The results demonstrated that: (1) The DR1 and DR2 were expressed in the bodies and axons of the SGN; (2) After the treatment with SS, the surface protein expressions of GABRα2 and NR1 were decreased by 44.69% and 21.57%, respectively, while the total protein expressions showed no significant changes; (3) Neither SS + SCH23390 (DR1 antagonist) group nor SS + Eticlopride (DR2 antagonist) group showed significant differences in GABRα2 and NR1 surface protein expressions compared with the control group. These results suggest that SS regulates the surface GABA A and NMDA receptors trafficking on SGN, and the mechanism may involve DR mediation.

  3. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

    International Nuclear Information System (INIS)

    Cohen, Samuel M.; Li, Boxing; Tsien, Richard W.; Ma, Huan

    2015-01-01

    Reliance on Ca 2+ signaling has been well-preserved through the course of evolution. While the complexity of Ca 2+ signaling pathways has increased, activation of transcription factors including CREB by Ca 2+ /CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca 2+ sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca 2+ /CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling

  4. MCH and apomorphine in combination enhance action potential firing of nucleus accumbens shell neurons in vitro

    Directory of Open Access Journals (Sweden)

    F Woodward Hopf

    2013-04-01

    Full Text Available The MCH and dopamine receptor systems have been shown to modulate a number of behaviors related to reward processing, addiction, and neuropsychiatric conditions such as schizophrenia and depression. In addition, MCH and dopamine receptors can interact in a positive manner, for example in the expression of cocaine self-administration. A recent report (Chung et al., 2011a showed that the DA1/DA2 dopamine receptor activator apomorphine suppresses pre-pulse inhibition, a preclinical model for some aspects of schizophrenia. Importantly, MCH can enhance the effects of lower doses of apomorphine, suggesting that co-modulation of dopamine and MCH receptors might alleviate some symptoms of schizophrenia with a lower dose of dopamine receptor modulator and thus fewer potential side effects. Here, we investigated whether MCH and apomorphine could enhance action potential firing in vitro in the nucleus accumbens shell (NAshell, a region which has previously been shown to mediate some behavioral effects of MCH. Using whole-cell patch-clamp electrophysiology, we found that MCH, which has no effect on firing on its own, was able to increase NAshell firing when combined with a subthreshold dose of apomorphine. Further, this MCH/apomorphine increase in firing was prevented by an antagonist of either a DA1 or a DA2 receptor, suggesting that apomorphine acts through both receptor types to enhance NAshell firing. The MCH/apomorphine-mediated firing increase was also prevented by an MCH receptor antagonist or a PKA inhibitor. Taken together, our results suggest that MCH can interact with lower doses of apomorphine to enhance NAshell firing, and thus that MCH and apomorphine might interact in vivo within the NAshell to suppress pre-pulse inhibition.

  5. Evolutionary and functional perspectives on signaling from neuronal surface to nucleus

    Energy Technology Data Exchange (ETDEWEB)

    Cohen, Samuel M.; Li, Boxing; Tsien, Richard W., E-mail: richard.tsien@nyumc.org; Ma, Huan, E-mail: mahuan@gmail.com

    2015-04-24

    Reliance on Ca{sup 2+} signaling has been well-preserved through the course of evolution. While the complexity of Ca{sup 2+} signaling pathways has increased, activation of transcription factors including CREB by Ca{sup 2+}/CaM-dependent kinases (CaMKs) has remained critical for long-term plasticity. In C. elegans, the CaMK family is made up of only three members, and CREB phosphorylation is mediated by CMK-1, the homologue of CaMKI. CMK-1 nuclear translocation directly regulates adaptation of thermotaxis behavior in response to changes in the environment. In mammals, the CaMK family has been expanded from three to ten members, enabling specialization of individual elements of a signal transduction pathway and increased reliance on the CaMKII subfamily. This increased complexity enables private line communication between Ca{sup 2+} sources at the cell surface and specific cellular targets. Using both new and previously published data, we review the mechanism of a γCaMKII-CaM nuclear translocation. This intricate pathway depends on a specific role for multiple Ca{sup 2+}/CaM-dependent kinases and phosphatases: α/βCaMKII phosphorylates γCaMKII to trap CaM; CaN dephosphorylates γCaMKII to dispatch it to the nucleus; and PP2A induces CaM release from γCaMKII so that CaMKK and CaMKIV can trigger CREB phosphorylation. Thus, while certain basic elements have been conserved from C. elegans, evolutionary modifications offer opportunities for targeted communication, regulation of key nodes and checkpoints, and greater specificity and flexibility in signaling.

  6. Methamphetamine facilitates female sexual behavior and enhances neuronal activation in the medial amygdala and ventromedial nucleus of the hypothalamus.

    Science.gov (United States)

    Holder, Mary K; Hadjimarkou, Maria M; Zup, Susan L; Blutstein, Tamara; Benham, Rebecca S; McCarthy, Margaret M; Mong, Jessica A

    2010-02-01

    Methamphetamine (MA) abuse has reached epidemic proportions in the United States. Users of MA report dramatic increases in sexual drive that have been associated with increased engagement in risky sexual behavior leading to higher rates of sexually transmitted diseases and unplanned pregnancies. The ability of MA to enhance sexual drive in females is enigmatic since related psychostimulants like amphetamine and cocaine appear not to affect sexual drive in women, and in rodents models, amphetamine has been reported to be inhibitory to female sexual behavior. Examination of MA's effects on female sexual behavior in an animal model is lacking. Here, using a rodent model, we have demonstrated that MA enhanced female sexual behavior. MA (5mg/kg) or saline vehicle was administered once daily for 3 days to adult ovariectomized rats primed with ovarian steroids. MA treatment significantly increased the number of proceptive events and the lordosis response compared to hormonally primed, saline controls. The effect of MA on the neural circuitry underlying the motivation for sexual behavior was examined using Fos immunoreactivity. In the medial amygdala and the ventromedial nucleus of the hypothalamus, nuclei implicated in motivated behaviors, ovarian hormones and MA independently enhance the neuronal activation, but more striking was the significantly greater activation induced by their combined administration. Increases in dopamine neurotransmission may underlie the MA/hormone mediated increase in neuronal activation. In support of this possibility, ovarian hormones significantly increased tyrosine hydroxylase (the rate limiting enzyme in dopamine synthesis) immunoreactivity in the medial amygdala. Thus our present data suggest that the interactions of MA and ovarian hormones leads to changes in the neural substrate of key nuclei involved in mediating female sexual behaviors, and these changes may underlie MA's ability to enhance these behaviors. 2009 Elsevier Ltd. All

  7. ERG voltage-gated K+ channels regulate excitability and discharge dynamics of the medial vestibular nucleus neurones.

    Science.gov (United States)

    Pessia, Mauro; Servettini, Ilenio; Panichi, Roberto; Guasti, Leonardo; Grassi, Silvarosa; Arcangeli, Annarosa; Wanke, Enzo; Pettorossi, Vito Enrico

    2008-10-15

    The discharge properties of the medial vestibular nucleus neurones (MVNn) critically depend on the activity of several ion channel types. In this study we show, immunohistochemically, that the voltage-gated K(+) channels ERG1A, ERG1B, ERG2 and ERG3 are highly expressed within the vestibular nuclei of P10 and P60 mice. The role played by these channels in the spike-generating mechanisms of the MVNn and in temporal information processing was investigated electrophysiologically from mouse brain slices, in vitro, by analysing the spontaneous discharge and the response to square-, ramp- and sinusoid-like intracellular DC current injections in extracellular and whole-cell patch-clamp studies. We show that more than half of the recorded MVNn were responsive to ERG channel block (WAY-123,398, E4031), displaying an increase in spontaneous activity and discharge irregularity. The response to step and ramp current injection was also modified by ERG block showing a reduction of first spike latency, enhancement of discharge rate and reduction of the slow spike-frequency adaptation process. ERG channels influence the interspike slope without affecting the spike shape. Moreover, in response to sinusoid-like current, ERG channel block caused frequency-dependent gain enhancement and phase-lead shift. Taken together, the data demonstrate that ERG channels control the excitability of MVNn, their discharge regularity and probably their resonance properties.

  8. Functional and neurochemical characterization of angiotensin type 1A receptor-expressing neurons in the nucleus of the solitary tract of the mouse.

    Science.gov (United States)

    Carter, D A; Choong, Y-T; Connelly, A A; Bassi, J K; Hunter, N O; Thongsepee, N; Llewellyn-Smith, I J; Fong, A Y; McDougall, S J; Allen, A M

    2017-10-01

    Angiotensin II acts via two main receptors within the central nervous system, with the type 1A receptor (AT 1A R) most widely expressed in adult neurons. Activation of the AT 1 R in the nucleus of the solitary tract (NTS), the principal nucleus receiving central synapses of viscerosensory afferents, modulates cardiovascular reflexes. Expression of the AT 1 R occurs in high density within the NTS of most mammals, including humans, but the fundamental electrophysiological and neurochemical characteristics of the AT 1A R-expressing NTS neurons are not known. To address this, we have used a transgenic mouse, in which the AT 1A R promoter drives expression of green fluorescent protein (GFP). Approximately one-third of AT 1A R-expressing neurons express the catecholamine-synthetic enzyme tyrosine hydroxylase (TH), and a subpopulation of these stained for the transcription factor paired-like homeobox 2b (Phox2b). A third group, comprising approximately two-thirds of the AT 1A R-expressing NTS neurons, showed Phox2b immunoreactivity alone. A fourth group in the ventral subnucleus expressed neither TH nor Phox2b. In whole cell recordings from slices in vitro, AT 1A R-GFP neurons exhibited voltage-activated potassium currents, including the transient outward current and the M-type potassium current. In two different mouse strains, both AT 1A R-GFP neurons and TH-GFP neurons showed similar AT 1A R-mediated depolarizing responses to superfusion with angiotensin II. These data provide a comprehensive description of AT 1A R-expressing neurons in the NTS and increase our understanding of the complex actions of this neuropeptide in the modulation of viscerosensory processing. Copyright © 2017 the American Physiological Society.

  9. Cochlear Implants

    Science.gov (United States)

    ... NIDCD A cochlear implant is a small, complex electronic device that can help to provide a sense ... Hearing Aids Retinitis Pigmentosa - National Eye Institute Telecommunications Relay Services Usher Syndrome Your Baby's Hearing Screening News ...

  10. Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus? [v1; ref status: indexed, http://f1000r.es/TYJStu

    OpenAIRE

    Miriam Matamales

    2012-01-01

    Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucle...

  11. Cochlear implant magnet retrofit.

    Science.gov (United States)

    Cohen, N L; Breda, S D; Hoffman, R A

    1988-06-01

    An implantable magnet is now available for patients who have received the standard Nucleus 22-channel cochlear implant and who are not able to wear the headband satisfactorily. This magnet is attached in piggy-back fashion to the previously implanted receiver/stimulator by means of a brief operation under local anesthesia. Two patients have received this magnet retrofit, and are now wearing the headset with greater comfort and satisfaction. It is felt that the availability of this magnet will increase patient compliance in regard to hours of implant usage.

  12. The median preoptic nucleus reciprocally modulates activity of arousal-related and sleep-related neurons in the perifornical lateral hypothalamus.

    Science.gov (United States)

    Suntsova, Natalia; Guzman-Marin, Ruben; Kumar, Sunil; Alam, Md Noor; Szymusiak, Ronald; McGinty, Dennis

    2007-02-14

    The perifornical-lateral hypothalamic area (PF/LH) contains neuronal groups playing an important role in control of waking and sleep. Among the brain regions that regulate behavioral states, one of the strongest sources of projections to the PF/LH is the median preoptic nucleus (MnPN) containing a sleep-active neuronal population. To evaluate the role of MnPN afferents in the control of PF/LH neuronal activity, we studied the responses of PF/LH cells to electrical stimulation or local chemical manipulation of the MnPN in freely moving rats. Single-pulse electrical stimulation evoked responses in 79% of recorded PF/LH neurons. No cells were activated antidromically. Direct and indirect transsynaptic effects depended on sleep-wake discharge pattern of PF/LH cells. The majority of arousal-related neurons, that is, cells discharging at maximal rates during active waking (AW) or during AW and rapid eye movement (REM) sleep, exhibited exclusively or initially inhibitory responses to stimulation. Sleep-related neurons, the cells with elevated discharge during non-REM and REM sleep or selectively active in REM sleep, exhibited exclusively or initially excitatory responses. Activation of the MnPN via microdialytic application of L-glutamate or bicuculline resulted in reduced discharge of arousal-related and in excitation of sleep-related PF/LH neurons. Deactivation of the MnPN with muscimol caused opposite effects. The results indicate that the MnPN contains subset(s) of neurons, which exert inhibitory control over arousal-related and excitatory control over sleep-related PF/LH neurons. We hypothesize that MnPN sleep-active neuronal group has both inhibitory and excitatory outputs that participate in the inhibitory control of arousal-promoting PF/LH mechanisms.

  13. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity.

    Science.gov (United States)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P M; Swaab, Dick F

    2011-10-15

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir) neurons in relation to sex, age, and gender identity in the postmortem brain of 77 subjects. First we compared the InM volume and number of Gal-Ir neurons of 22 males and 22 females in the course of aging. In a second experiment, we compared for the first time the InM volume and the total and Gal-Ir neuron number in 43 subjects with different gender identities: 14 control males (M), 11 control females (F), 10 male-to-female (MtF) transsexual people, and 5 men who were castrated because of prostate cancer (CAS). In the first experiment we found a sex difference in the younger age group ( 45 years. In the second experiment the MtF transsexual group presented an intermediate value for the total InM neuron number and volume that did not seem different in males and females. Because the CAS group did not have total neuron numbers that were different from the intact males, the change in adult circulating testosterone levels does not seem to explain the intermediate values in the MtF group. Organizational and activational hormone effects on the InM are discussed. Copyright © 2011 Wiley-Liss, Inc.

  14. Onuf's nucleus X

    DEFF Research Database (Denmark)

    Schrøder, H D

    1981-01-01

    in the length of the nucleus was observed. Based on the cytoarchitecture the nucleus could be divided in three parts, a cranial, a dorsomedial and a ventrolateral. All parts of the nucleus consisted of chromatin-rich medium-sized neurons, and apparent direct appositions between different cells bodies as well...

  15. Direct Reprogramming of Spiral Ganglion Non-neuronal Cells into Neurons: Toward Ameliorating Sensorineural Hearing Loss by Gene Therapy

    Directory of Open Access Journals (Sweden)

    Teppei Noda

    2018-02-01

    Full Text Available Primary auditory neurons (PANs play a critical role in hearing by transmitting sound information from the inner ear to the brain. Their progressive degeneration is associated with excessive noise, disease and aging. The loss of PANs leads to permanent hearing impairment since they are incapable of regenerating. Spiral ganglion non-neuronal cells (SGNNCs, comprised mainly of glia, are resident within the modiolus and continue to survive after PAN loss. These attributes make SGNNCs an excellent target for replacing damaged PANs through cellular reprogramming. We used the neurogenic pioneer transcription factor Ascl1 and the auditory neuron differentiation factor NeuroD1 to reprogram SGNNCs into induced neurons (iNs. The overexpression of both Ascl1 and NeuroD1 in vitro generated iNs at high efficiency. Transcriptome analyses revealed that iNs displayed a transcriptome profile resembling that of endogenous PANs, including expression of several key markers of neuronal identity: Tubb3, Map2, Prph, Snap25, and Prox1. Pathway analyses indicated that essential pathways in neuronal growth and maturation were activated in cells upon neuronal induction. Furthermore, iNs extended projections toward cochlear hair cells and cochlear nucleus neurons when cultured with each respective tissue. Taken together, our study demonstrates that PAN-like neurons can be generated from endogenous SGNNCs. This work suggests that gene therapy can be a viable strategy to treat sensorineural hearing loss caused by degeneration of PANs.

  16. Intracellular postsynaptic cannabinoid receptors link thyrotropin-releasing hormone receptors to TRPC-like channels in thalamic paraventricular nucleus neurons.

    Science.gov (United States)

    Zhang, L; Kolaj, M; Renaud, L P

    2015-12-17

    In rat thalamic paraventricular nucleus of thalamus (PVT) neurons, activation of thyrotropin-releasing hormone (TRH) receptors enhances excitability via concurrent decrease in G protein-coupled inwardly-rectifying potassium (GIRK)-like and activation of transient receptor potential cation (TRPC)4/5-like cationic conductances. An exploration of intracellular signaling pathways revealed the TRH-induced current to be insensitive to phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, but reduced by D609, an inhibitor of phosphatidylcholine-specific PLC (PC-PLC). A corresponding change in the I-V relationship implied suppression of the cationic component of the TRH-induced current. Diacylglycerol (DAG) is a product of the hydrolysis of PC. Studies focused on the isolated cationic component of the TRH-induced response revealed a reduction by RHC80267, an inhibitor of DAG lipase, the enzyme involved in the hydrolysis of DAG to the endocannabinoid 2-arachidonoylglycerol (2-AG). Further investigation revealed enhancement of the cationic component in the presence of either JZL184 or WWL70, inhibitors of enzymes involved in the hydrolysis of 2-AG. A decrease in the TRH-induced response was noted in the presence of rimonabant or SR144528, membrane permeable CB1 and CB2 receptor antagonists, respectively. A decrease in the TRH-induced current by intracellular, but not by bath application of the membrane impermeable peptide hemopressin, selective for CB1 receptors, suggests a postsynaptic intracellular localization of these receptors. The TRH-induced current was increased in the presence of arachidonyl-2'-chloroethylamide (ACEA) or JWH133, CB1 and CB2 receptor agonists, respectively. The PI3-kinase inhibitor LY294002, known to inhibit TRPC translocation, decreased the response to TRH. In addition, a TRH-induced enhancement of the low-threshold spike was prevented by both rimonabant, and SR144528. TRH had no influence on excitatory or inhibitory miniature

  17. Optogenetic inhibition of D1R containing nucleus accumbens neurons alters cocaine- mediated regulation of Tiam1

    Directory of Open Access Journals (Sweden)

    Ramesh eChandra

    2013-05-01

    Full Text Available Exposure to psychostimulants results in structural and synaptic plasticity in striatal medium spiny neurons (MSNs. These cellular adaptations arise from alterations in genes that are highly implicated in the rearrangement of the actin cytoskeleton, such as Tiam1. Previous studies have demonstrated a crucial role for dopamine receptor 1 (D1-containing striatal MSNs in mediating psychostimulant induced plasticity changes. These D1-MSNs in the nucleus accumbens (NAc positively regulate drug seeking, reward, and locomotor behavioral effects as well as the morphological adaptations of psychostimulant drugs. Here, we demonstrate that rats that actively self-administer cocaine display reduced levels of Tiam1 in the NAc. To further examine the cell type specific contribution to these changes in Tiam1 we used optogenetics to selectively manipulate NAc D1-MSNs or dopamine receptor 2 (D2 expressing MSNs. We find that repeated ChR2 activation of D1-MSNs but not D2-MSNs caused a down-regulation of Tiam1 levels similar to the effects of cocaine. Further, activation of D2-MSNs, which caused a late blunted cocaine-mediated locomotor behavioral response, did not alter Tiam1 levels. We then examined the contribution of D1-MSNs to the cocaine-mediated decrease of Tiam1. Using the light activated chloride pump, eNpHR3.0, we selectively inhibited D1-MSNs during cocaine exposure, which resulted in a behavioral blockade of cocaine-induced locomotor sensitization. Moreover, inhibiting these NAc D1-MSNs during cocaine exposure reversed the down-regulation of Tiam1 gene expression and protein levels. These data demonstrate that altering activity in specific neural circuits with optogenetics can impact the underlying molecular substrates of psychostimulant mediated behavior and function.

  18. Sweet taste receptor serves to activate glucose- and leptin-responsive neurons in the hypothalamic arcuate nucleus and participates in glucose responsiveness.

    Directory of Open Access Journals (Sweden)

    Daisuke Kohno

    2016-11-01

    Full Text Available The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC: glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanism underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2 and taste type 1 receptor 3 (T1R3 and senses sweet tastes. T1R2 and T1R3 receptors are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10-5 M-10-2 M dose dependently increased [Ca2+]i in 12-16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentage of proopiomelanocortin (POMC neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular

  19. Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness.

    Science.gov (United States)

    Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

    2016-01-01

    The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10 -5 -10 -2 M dose dependently increased [Ca 2+ ] i in 12-16% of ARC neurons. The sucralose-induced [Ca 2+ ] i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca 2+ ] i increase was inhibited under an extracellular Ca 2+ -free condition and in the presence of an L-type Ca 2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation

  20. Acid-sensing ion channels expression, identity and role in the excitability of the cochlear afferent neurons

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    Antonia eGonzález-Garrido

    2015-12-01

    Full Text Available Acid-sensing ion channels (ASICs are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4 that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs. These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations and N,N,N’,N’–tetrakis-(2-piridilmetil-etilendiamina (TPEN increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2 and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs.

  1. Acid-Sensing Ion Channels Expression, Identity and Role in the Excitability of the Cochlear Afferent Neurons

    Science.gov (United States)

    González-Garrido, Antonia; Vega, Rosario; Mercado, Francisco; López, Iván A.; Soto, Enrique

    2015-01-01

    Acid-sensing ion channels (ASICs) are activated by an increase in the extracellular proton concentration. There are four genes (ASIC1-4) that encode six subunits, and they are involved in diverse neuronal functions, such as mechanosensation, learning and memory, nociception, and modulation of retinal function. In this study, we characterize the ASIC currents of spiral ganglion neurons (SGNs). These ASIC currents are primarily carried by Na+, exhibit fast activation and desensitization, display a pH50 of 6.2 and are blocked by amiloride, indicating that these are ASIC currents. The ASIC currents were further characterized using several pharmacological tools. Gadolinium and acetylsalicylic acid reduced these currents, and FMRFamide, zinc (at high concentrations) and N,N,N’,N’–tetrakis-(2-piridilmetil)-ethylenediamine increased them, indicating that functional ASICs are composed of the subunits ASIC1, ASIC2, and ASIC3. Neomycin and streptomycin reduced the desensitization rate of the ASIC current in SGNs, indicating that ASICs may contribute to the ototoxic action of aminoglycosides. RT-PCR of the spiral ganglion revealed significant expression of all ASIC subunits. By immunohistochemistry the expression of the ASIC1a, ASIC2a, ASIC2b, and ASIC3 subunits was detected in SGNs. Although only a few SGNs exhibited action potential firing in response to an acidic stimulus, protons in the extracellular solution modulated SGN activity during sinusoidal stimulation. Our results show that protons modulate the excitability of SGNs via ASICs. PMID:26733809

  2. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Science.gov (United States)

    Clément, Olivier; Valencia Garcia, Sara; Libourel, Paul-Antoine; Arthaud, Sébastien; Fort, Patrice; Luppi, Pierre-Hervé

    2014-01-01

    GABAergic neurons specifically active during paradoxical sleep (PS) localized in the dorsal paragigantocellular reticular nucleus (DPGi) are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  3. The inhibition of the dorsal paragigantocellular reticular nucleus induces waking and the activation of all adrenergic and noradrenergic neurons: a combined pharmacological and functional neuroanatomical study.

    Directory of Open Access Journals (Sweden)

    Olivier Clément

    Full Text Available GABAergic neurons specifically active during paradoxical sleep (PS localized in the dorsal paragigantocellular reticular nucleus (DPGi are known to be responsible for the cessation of activity of the noradrenergic neurons of the locus coeruleus during PS. In the present study, we therefore sought to determine the role of the DPGi in PS onset and maintenance and in the inhibition of the LC noradrenergic neurons during this state. The effect of the inactivation of DPGi neurons on the sleep-waking cycle was examined in rats by microinjection of muscimol, a GABAA agonist, or clonidine, an alpha-2 adrenergic receptor agonist. Combining immunostaining of the different populations of wake-inducing neurons with that of c-FOS, we then determined whether muscimol inhibition of the DPGi specifically induces the activation of the noradrenergic neurons of the LC. Slow wave sleep and PS were abolished during 3 and 5 h after muscimol injection in the DPGi, respectively. The application of clonidine in the DPGi specifically induced a significant decrease in PS quantities and delayed PS appearance compared to NaCl. We further surprisingly found out that more than 75% of the noradrenergic and adrenergic neurons of all adrenergic and noradrenergic cell groups are activated after muscimol treatment in contrast to the other wake active systems significantly less activated. These results suggest that, in addition to its already know inhibition of LC noradrenergic neurons during PS, the DPGi might inhibit the activity of noradrenergic and adrenergic neurons from all groups during PS, but also to a minor extent during SWS and waking.

  4. Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets.

    Science.gov (United States)

    Peris, Joanna; MacFadyen, Kaley; Smith, Justin A; de Kloet, Annette D; Wang, Lei; Krause, Eric G

    2017-04-01

    The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse. To phenotype OT-receptor (OTR) expressing neurons originating within the VTA, we delivered Cre-inducible adeno-associated virus that drives the expression of fluorescent marker into the VTA of male mice that had Cre-recombinase driven by OTR gene expression. OTR-expressing VTA neurons project to NAc, prefrontal cortex, the extended amygdala, and other forebrain regions but less than 10% of these OTR-expressing neurons were identified as DA neurons (defined by tyrosine hydroxylase colocalization). Instead, almost 50% of OTR-expressing cells in the VTA were glutamate (GLU) neurons, as indicated by expression of mRNA for the vesicular GLU transporter (vGluT). About one-third of OTR-expressing VTA neurons did not colocalize with either DA or GLU phenotypic markers. Thus, OTR expression by VTA neurons implicates that OT regulation of reward circuitry is more complex than a direct action on DA neurotransmission. J. Comp. Neurol. 525:1094-1108, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  5. Responses of Nucleus Tractus Solitarius (NTS) early and late neurons to blood pressure changes in anesthetized F344 rats.

    Science.gov (United States)

    Kolpakova, Jenya; Li, Liang; Hatcher, Jeffrey T; Gu, He; Zhang, Xueguo; Chen, Jin; Cheng, Zixi Jack

    2017-01-01

    Previously, many different types of NTS barosensitive neurons were identified. However, the time course of NTS barosensitive neuronal activity (NA) in response to arterial pressure (AP) changes, and the relationship of NA-AP changes, have not yet been fully quantified. In this study, we made extracellular recordings of single NTS neurons firing in response to AP elevation induced by occlusion of the descending aorta in anesthetized rats. Our findings were that: 1) Thirty-five neurons (from 46 neurons) increased firing, whereas others neurons either decreased firing upon AP elevation, or were biphasic: first decreased firing upon AP elevation and then increased firing during AP decrease. 2) Fourteen neurons with excitatory responses were activated and rapidly increased their firing during the early phase of AP increase (early neurons); whereas 21 neurons did not increase firing until the mean arterial pressure changes (ΔMAP) reached near/after the peak (late neurons). 3) The early neurons had a significantly higher firing rate than late neurons during AP elevation at a similar rate. 4) Early neuron NA-ΔMAP relationship could be well fitted and characterized by the sigmoid logistic function with the maximal gain of 29.3. 5) The increase of early NA correlated linearly with the initial heart rate (HR) reduction. 6) The late neurons did not contribute to the initial HR reduction. However, the late NA could be well correlated with HR reduction during the late phase. Altogether, our study demonstrated that the NTS excitatory neurons could be grouped into early and late neurons based on their firing patterns. The early neurons could be characterized by the sigmoid logistic function, and different neurons may differently contribute to HR regulation. Importantly, the grouping and quantitative methods used in this study may provide a useful tool for future assessment of functional changes of early and late neurons in disease models.

  6. Influence of age-related changes in nitric oxide synthase-expressing neurons in the rat supraoptic nucleus on inhibition of salivary secretion.

    Science.gov (United States)

    Tanaka, Takehiko; Tamada, Yoshitaka; Suwa, Fumihiko

    2008-02-01

    Age-related inhibition of salivary secretion has been demonstrated in rats, and the nitric oxide (NO) present in the supraoptic nucleus (SON) and the medial septal area has been reported to play an inhibitory role in the regulation of salivary secretion. In the present study, we investigated the age-related changes occurring in the NO synthase (NOS)-expressing neurons in the SON, which is related to the production of NO, and discussed the interrelation between the age-related changes in the NOS-expressing neurons and the age-related inhibition of salivary secretion. Nissl staining and reduced nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry were performed for young adult and aged rats. Quantitative analysis was also performed using the Nissl-stained and NADPH-d-positive neurons. Although the numbers of the Nissl-stained neurons did not change, significant age-related increases were detected in cell number, cell size and reactive density of the NADPH-d-positive neurons. Therefore, the production of NO in the SON neurons increased with age. We concluded that the age-related increase in the NO in the SON might be a factor that contributes to the age-related inhibition of salivary secretion.

  7. Variable Action Potential Backpropagation during Tonic Firing and Low-Threshold Spike Bursts in Thalamocortical But Not Thalamic Reticular Nucleus Neurons.

    Science.gov (United States)

    Connelly, William M; Crunelli, Vincenzo; Errington, Adam C

    2017-05-24

    Backpropagating action potentials (bAPs) are indispensable in dendritic signaling. Conflicting Ca 2+ -imaging data and an absence of dendritic recording data means that the extent of backpropagation in thalamocortical (TC) and thalamic reticular nucleus (TRN) neurons remains unknown. Because TRN neurons signal electrically through dendrodendritic gap junctions and possibly via chemical dendritic GABAergic synapses, as well as classical axonal GABA release, this lack of knowledge is problematic. To address this issue, we made two-photon targeted patch-clamp recordings from rat TC and TRN neuron dendrites to measure bAPs directly. These recordings reveal that "tonic"' and low-threshold-spike (LTS) "burst" APs in both cell types are always recorded first at the soma before backpropagating into the dendrites while undergoing substantial distance-dependent dendritic amplitude attenuation. In TC neurons, bAP attenuation strength varies according to firing mode. During LTS bursts, somatic AP half-width increases progressively with increasing spike number, allowing late-burst spikes to propagate more efficiently into the dendritic tree compared with spikes occurring at burst onset. Tonic spikes have similar somatic half-widths to late burst spikes and undergo similar dendritic attenuation. In contrast, in TRN neurons, AP properties are unchanged between LTS bursts and tonic firing and, as a result, distance-dependent dendritic attenuation remains consistent across different firing modes. Therefore, unlike LTS-associated global electrical and calcium signals, the spatial influence of bAP signaling in TC and TRN neurons is more restricted, with potentially important behavioral-state-dependent consequences for synaptic integration and plasticity in thalamic neurons. SIGNIFICANCE STATEMENT In most neurons, action potentials (APs) initiate in the axosomatic region and propagate into the dendritic tree to provide a retrograde signal that conveys information about the level of

  8. Expression of ankyrin repeat and suppressor of cytokine signaling box protein 4 (Asb-4) in proopiomelanocortin neurons of the arcuate nucleus of mice produces a hyperphagic, lean phenotype.

    Science.gov (United States)

    Li, Ji-Yao; Chai, Biao-Xin; Zhang, Weizhen; Wang, Hui; Mulholland, Michael W

    2010-01-01

    Ankyrin repeat and suppressor of cytokine signaling box-containing protein 4 (Asb-4) is specifically expressed in the energy homeostasis-related brain areas and colocalizes with proopiomelanocortin (POMC) neurons of the arcuate nucleus (ARC). Injection of insulin into the third ventricle of the rat brain increased Asb-4 mRNA expression in the paraventricular nucleus but not in the ARC of the hypothalamus, whereas injection of leptin (ip) increased Asb-4 expression in both mouse paraventricular nucleus and ARC. A transgenic mouse in which Myc-tagged Asb-4 is specifically expressed in POMC neurons of the ARC was made and used to study the effects of Asb-4 on ingestive behavior and metabolic rate. Animals with overexpression of Asb-4 in POMC neurons demonstrated an increase in food intake. However, POMC-Asb-4 transgenic animals gained significantly less weight from 6-30 wk of age. The POMC-Asb-4 mice had reduced fat mass and increased lean mass and lower levels of blood leptin. The transgenic animals were resistant to high-fat diet-induced obesity. Transgenic mice had significantly higher rates of oxygen consumption and carbon dioxide production than wild-type mice during both light and dark periods. The locomotive activity of transgenic mice was increased. The overexpression of Asb-4 in POMC neurons increased POMC mRNA expression in the ARC. The transgenic animals had no observed effect on peripheral glucose metabolism and the activity of the autonomic nervous system. These results indicate that Asb-4 is a key regulatory protein in the central nervous system, involved in the control of feeding behavior and metabolic rate.

  9. Neural control of left ventricular contractility in the dog heart: synaptic interactions of negative inotropic vagal preganglionic neurons in the nucleus ambiguus with tyrosine hydroxylase immunoreactive terminals.

    Science.gov (United States)

    Massari, V J; Dickerson, L W; Gray, A L; Lauenstein, J M; Blinder, K J; Newsome, J T; Rodak, D J; Fleming, T J; Gatti, P J; Gillis, R A

    1998-08-17

    Recent physiological evidence indicates that vagal postganglionic control of left ventricular contractility is mediated by neurons found in a ventricular epicardial fat pad ganglion. In the dog this region has been referred to as the cranial medial ventricular (CMV) ganglion [J.L. Ardell, Structure and function of mammalian intrinsic cardiac neurons, in: J.A. Armour, J.L. Ardell (Eds.). Neurocardiology, Oxford Univ. Press, New York, 1994, pp. 95-114; B.X. Yuan, J.L. Ardell, D.A. Hopkins, A.M. Losier, J.A. Armour, Gross and microscopic anatomy of the canine intrinsic cardiac nervous system, Anat. Rec., 239 (1994) 75-87]. Since activation of the vagal neuronal input to the CMV ganglion reduces left ventricular contractility without influencing cardiac rate or AV conduction, this ganglion contains a functionally selective pool of negative inotropic parasympathetic postganglionic neurons. In the present report we have defined the light microscopic distribution of preganglionic negative inotropic neurons in the CNS which are retrogradely labeled from the CMV ganglion. Some tissues were also processed for the simultaneous immunocytochemical visualization of tyrosine hydroxylase (TH: a marker for catecholaminergic neurons) and examined with both light microscopic and electron microscopic methods. Histochemically visualized neurons were observed in a long slender column in the ventrolateral nucleus ambiguus (NA-VL). The greatest number of retrogradely labeled neurons were observed just rostral to the level of the area postrema. TH perikarya and dendrites were commonly observed interspersed with vagal motoneurons in the NA-VL. TH nerve terminals formed axo-dendritic synapses upon negative inotropic vagal motoneurons, however the origin of these terminals remains to be determined. We conclude that synaptic interactions exist which would permit the parasympathetic preganglionic vagal control of left ventricular contractility to be modulated monosynaptically by

  10. Neurons in red nucleus and primary motor cortex exhibit similar responses to mechanical perturbations applied to the upper-limb during posture

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    Troy Michael Herter

    2015-04-01

    Full Text Available Primary motor cortex (M1 and red nucleus (RN are brain regions involved in limb motor control. Both structures are highly interconnected with the cerebellum and project directly to the spinal cord, although the contribution of RN is smaller than M1. It remains uncertain whether RN and M1 serve similar or distinct roles during posture and movement. Many neurons in M1 respond rapidly to mechanical disturbances of the limb, but it remains unclear whether RN neurons also respond to such limb perturbations. We have compared discharges of single neurons in RN (n = 49 and M1 (n = 109 of one monkey during a postural perturbation task. Neural responses to whole-limb perturbations were examined by transiently applying (300 ms flexor or extensor torques to the shoulder and/or elbow while the monkeys attempted to maintain a static hand posture. Relative to baseline discharges before perturbation onset, perturbations evoked rapid (<100 ms changes of neural discharges in many RN (28 of 49, 57% and M1 (43 of 109, 39% neurons. In addition to exhibiting a greater proportion of perturbation-related neurons, RN neurons also tended to exhibit higher peak discharge frequencies in response to perturbations than M1 neurons. Importantly, neurons in both structures exhibited similar response latencies and tuning properties (preferred torque directions and tuning widths in joint-torque space. Proximal arm muscles also displayed similar tuning properties in joint-torque space. These results suggest that RN is more sensitive than M1 to mechanical perturbations applied during postural control but both structures may play a similar role in feedback control of posture.

  11. Behavioral Flexibility Is Increased by Optogenetic Inhibition of Neurons in the Nucleus Accumbens Shell during Specific Time Segments

    Science.gov (United States)

    Aquili, Luca; Liu, Andrew W.; Shindou, Mayumi; Shindou, Tomomi; Wickens, Jeffery R.

    2014-01-01

    Behavioral flexibility is vital for survival in an environment of changing contingencies. The nucleus accumbens may play an important role in behavioral flexibility, representing learned stimulus-reward associations in neural activity during response selection and learning from results. To investigate the role of nucleus accumbens neural activity…

  12. 18F-FDG PET imaging on the neuronal network of Parkinson's disease patients following deep brain stimulation of bilateral subthalamic nucleus

    International Nuclear Information System (INIS)

    Zuo Chuantao; Huang Zhemin; Zhao Jun; Guan Yihui; Lin Xiangtong; Li Dianyou; Sun Bomin

    2007-01-01

    Objective: There is evidence that the cause and progression of Parkinson's disease (PD) may be attributed to subthalamic nucleus (STN) dysfunction and that external electrical stimulation of the STN may improve the underlying neuronal network. This study aimed at using 18 F-FDG PET to monitor the functional status of the neuronal network of advanced PD patients following deep brain stimulation (DBS) of bilateral STN. Methods: Five PD patients in advanced stage, rated according to unified PD rat- ing scale (UPDRS) motion score, underwent bilateral STN DBS implantation. Six months after the implantation, each patient was studied with 18 F-FDG PET scans under stimulation turned 'on' and 'off' conditions. Statistical parametric mapping 2 (SPM2) was applied for data analyses. Results: Bilateral STN DBS reduced glucose utilization in lentiform nucleus (globus pallidus), bilateral thalamus, cerebellum, as well as the distal parietal cortex. However, glucose utilization in midbrain and pons was increased. The PD-related pattern (PDRP) scores were significantly different during the 'on' status (2.12 ± 15.24) and 'off' status (4.93 ± 13.01), which corresponded to the clinical improvement of PD symptoms as PDRP scores decreased. Conclusion: 18 F-FDG PET may be useful in monitoring and mapping the metabolism of the neuronal network during bilateral STN DBS, thus supporting its therapeutic impact on PD patients. (authors)

  13. Neuronal activity-regulated gene transcription: how are distant synaptic signals conveyed to the nucleus? [v1; ref status: indexed, http://f1000r.es/TYJStu

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    Miriam Matamales

    2012-12-01

    Full Text Available Synaptic activity can trigger gene expression programs that are required for the stable change of neuronal properties, a process that is essential for learning and memory. Currently, it is still unclear how the stimulation of dendritic synapses can be coupled to transcription in the nucleus in a timely way given that large distances can separate these two cellular compartments. Although several mechanisms have been proposed to explain long distance communication between synapses and the nucleus, the possible co-existence of these models and their relevance in physiological conditions remain elusive. One model suggests that synaptic activation triggers the translocation to the nucleus of certain transcription regulators localised at postsynaptic sites that function as synapto-nuclear messengers. Alternatively, it has been hypothesised that synaptic activity initiates propagating regenerative intracellular calcium waves that spread through dendrites into the nucleus where nuclear transcription machinery is thereby regulated. It has also been postulated that membrane depolarisation of voltage-gated calcium channels on the somatic membrane is sufficient to increase intracellular calcium concentration and activate transcription without the need for transported signals from distant synapses. Here I provide a critical overview of the suggested mechanisms for coupling synaptic stimulation to transcription, the underlying assumptions behind them and their plausible physiological significance.

  14. Dispersion of the intrinsic neuronal periods affects the relationship of the entrainment range to the coupling strength in the suprachiasmatic nucleus

    Science.gov (United States)

    Gu, Changgui; Yang, Huijie; Wang, Man

    2017-11-01

    Living beings on the Earth are subjected to and entrained (synchronized) to the natural 24-h light-dark cycle. Interestingly, they can also be entrained to an external artificial cycle of non-24-h periods. The range of these periods is called the entrainment range and it differs among species. In mammals, the entrainment range is regulated by a main clock located in the suprachiasmatic nucleus (SCN) which is composed of 10 000 neurons in the brain. Previous works have found that the entrainment range depends on the cellular coupling strength in the SCN. In particular, the entrainment range decreases with the increase of the cellular coupling strength, provided that all the neuronal oscillators are identical. However, the SCN neurons differ in the intrinsic periods that follow a normal distribution in a range from 22 to 28 h. In the present study, taking the dispersion of the intrinsic neuronal periods into account, we examined the relationship between the entrainment range and the coupling strength. Results from numerical simulations and theoretical analyses both show that the relationship is altered to be paraboliclike if the intrinsic neuronal periods are nonidentical, and the maximal entrainment range is obtained with a suitable coupling strength. Our results shed light on the role of the cellular coupling in the entrainment ability of the SCN network.

  15. Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol.

    Science.gov (United States)

    Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J; Krumm, Elizabeth A; Yang, Jennifer A; Magby, Jason; Hu, Pu; Roepke, Troy A

    2016-02-15

    Ghrelin's receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Inhibition of swallowing reflex following phosphorylation of extracellular signal-regulated kinase in nucleus tractus solitarii neurons in rats with masseter muscle nociception.

    Science.gov (United States)

    Tsujimura, Takanori; Kitagawa, Junichi; Ueda, Koichiro; Iwata, Koichi

    2009-02-06

    Pain is associated with swallowing abnormalities in dysphagic patients. Understanding neuronal mechanisms underlying the swallowing abnormalities associated with orofacial abnormal pain is crucial for developing new methods to treat dysphagic patients. However, how the orofacial abnormal pain is involved in the swallowing abnormalities is not known. In order to evaluate neuronal mechanisms of modulation of the swallows by masticatory muscle pain, here we first induced swallows by topical administration of distilled water to the pharyngolaryngeal region. The swallowing reflex was significantly inhibited after capsaicin (10, 30mM) injection into the masseter muscle compared to vehicle injection. Moreover the number of phosphorylated extracellular signal-regulated kinase-like immunoreactive (pERK-LI) neurons in the nucleus tractus solitarii (NTS) was significantly increased in the rats with capsaicin injection into the masseter muscle compared to that with vehicle injection. Rostro-caudal distribution of pERK-LI neurons in the NTS was peaked at the obex level. The capsaicin-induced inhibitory effect on swallowing reflex was reversed after intrathecal administration of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor, PD98059. The present findings suggest that phosphorylation of ERK in NTS neurons may be involved in capsaicin-induced inhibition of swallowing reflex.

  17. Differential gene regulation of GHSR signaling pathway in the arcuate nucleus and NPY neurons by fasting, diet-induced obesity, and 17β-estradiol

    Science.gov (United States)

    Yasrebi, Ali; Hsieh, Anna; Mamounis, Kyle J.; Krumm, Elizabeth A.; Yang, Jennifer A.; Magby, Jason; Hu, Pu; Roepke, Troy A.

    2015-01-01

    Ghrelin’s receptor, growth hormone secretagogue receptor (GHSR), is highly expressed in the arcuate nucleus (ARC) and in neuropeptide Y (NPY) neurons. Fasting, diet-induced obesity (DIO), and 17β-estradiol (E2) influence ARC Ghsr expression. It is unknown if these effects occur in NPY neurons. Therefore, we examined the expression of Npy, Agrp, and GHSR signaling pathway genes after fasting, DIO, and E2 replacement in ARC and pools of NPY neurons. In males, fasting increased ARC Ghsr and NPY Foxo1 but decreased NPY Ucp2. In males, DIO decreased ARC and NPY Ghsr and Cpt1c. In fed females, E2 increased Agrp, Ghsr, Cpt1c, and Foxo1 in ARC. In NPY pools, E2 decreased Foxo1 in fed females but increased Foxo1 in fasted females. DIO in females suppressed Agrp and augmented Cpt1c in NPY neurons. In summary, genes involved in GHSR signaling are differentially regulated between the ARC and NPY neurons in a sex-dependent manner. PMID:26577678

  18. Acupuncture-like stimulation at auricular point Heart evokes cardiovascular inhibition via activating the cardiac-related neurons in the nucleus tractus solitarius.

    Science.gov (United States)

    Gao, Xin Yan; Li, Yan Hua; Liu, Kun; Rong, Pei Jing; Ben, Hui; Li, Liang; Zhu, Bing; Zhang, Shi Ping

    2011-06-23

    Fifty-eight male Sprague-Dawley rats used in the present study to investigate the role of baroreceptor sensitive neurons of the nucleus tractus solitarius (NTS) in the regulation of cardiovascular inhibition during acupuncture at the auricular point Heart, single unit recording was made in anesthetized Sprague-Dawley rats. A neuron was considered to be excited or inhibited by acupuncture stimulation if it displayed 15% more or less spikes s(-1), respectively. NTS neurons were classified into cardiac-related (CR) neurons and non-cardiac-related neurons based on whether their rhythmic discharges were synchronized with the R-waves and responding to sodium nitroprusside (NP; 20 μg/kg, i.v.) administration. Manual acupuncture was applied at the auricular point Heart and somatic acupuncture points ST36 and PC6. Acupuncture at auricular point Heart showed a more significant inhibitory effect on arterial pressure (-22.1±2.4mm Hg; Pheart rate (-12.7±1.7 bpm; PHeart also increased the level of response of CR neurons in the NTS (93.8%±26.0% increase in discharge rate; Pneurons evoked by auricular acupuncture, but had no effect on the same responses evoked by somatic acupuncture. Inactivation of the NTS with local anesthetics also decreased the cardiovascular inhibitory responses evoked by auricular acupuncture. Our results show that acupuncture at the auricular point Heart regulates cardiovascular function by activating baroreceptor sensitive neurons in the NTS in a similar manner as the baroreceptor reflex in cardiovascular inhibition. Copyright © 2011 Elsevier B.V. All rights reserved.

  19. Connections between EM2-containing terminals and GABA/μ-opioid receptor co-expressing neurons in the rat spinal trigeminal caudal nucleus

    Science.gov (United States)

    Li, Meng-Ying; Wu, Zhen-Yu; Lu, Ya-Cheng; Yin, Jun-Bin; Wang, Jian; Zhang, Ting; Dong, Yu-Lin; Wang, Feng

    2014-01-01

    Endomorphin-2 (EM2) demonstrates a potent antinociceptive effect via the μ-opioid receptor (MOR). To provide morphological evidence for the pain control effect of EM2, the synaptic connections between EM2-immunoreactive (IR) axonal terminals and γ-amino butyric acid (GABA)/MOR co-expressing neurons in lamina II of the spinal trigeminal caudal nucleus (Vc) were investigated in the rat. Dense EM2-, MOR- and GABA-IR fibers and terminals were mainly observed in lamina II of the Vc. Within lamina II, GABA- and MOR-neuronal cell bodies were also encountered. The results of immunofluorescent histochemical triple-staining showed that approximately 14.2 or 18.9% of GABA-IR or MOR-IR neurons also showed MOR- or GABA-immunopositive staining in lamina II; approximately 45.2 and 36.1% of the GABA-IR and MOR-IR neurons, respectively, expressed FOS protein in their nuclei induced by injecting formalin into the left lower lip of the mouth. Most of the GABA/MOR, GABA/FOS, and MOR/FOS double-labeled neurons made close contacts with EM2-IR fibers and terminals. Immuno-electron microscopy confirmed that the EM2-IR terminals formed synapses with GABA-IR or MOR-IR dendritic processes and neuronal cell bodies in lamina II of the Vc. These results suggest that EM2 might participate in pain transmission and modulation by binding to MOR-IR and GABAergic inhibitory interneuron in lamina II of the Vc to exert inhibitory effect on the excitatory interneuron in lamina II and projection neurons in laminae I and III. PMID:25386121

  20. Glycemic state regulates melanocortin, but not nesfatin-1, responsiveness of glucose-sensing neurons in the nucleus of the solitary tract.

    Science.gov (United States)

    Mimee, Andrea; Ferguson, Alastair V

    2015-04-15

    The nucleus of the solitary tract (NTS) is a medullary integrative center with critical roles in the coordinated control of energy homeostasis. Here, we used whole cell current-clamp recordings on rat NTS neurons in slice preparation to identify the presence of physiologically relevant glucose-sensing neurons. The majority of NTS neurons (n = 81) were found to be glucose-responsive, with 35% exhibiting a glucose-excited (GE) phenotype (mean absolute change in membrane potential: 9.5 ± 1.1 mV), and 21% exhibiting a glucose-inhibited (GI) response (mean: 6.3 ± 0.7 mV). Furthermore, we found glucose-responsive cells are preferentially influenced by the anorexigenic peptide α-melanocyte-stimulating hormone (α-MSH), but not nesfatin-1. Accordingly, alterations in glycemic state have profound effects on the responsiveness of NTS neurons to α-MSH, but not to nesfatin-1. Indeed, NTS neurons showed increasing responsiveness to α-MSH as extracellular glucose concentrations were decreased, and in hypoglycemic conditions, all NTS neurons were depolarized by α-MSH (mean 10.6 ± 3.2 mV; n = 8). Finally, decreasing levels of extracellular glucose correlated with a significant hyperpolarization of the baseline membrane potential of NTS neurons, highlighting the modulatory effect of glucose on the baseline excitability of cells in this region. Our findings reveal individual NTS cells are capable of integrating multiple sources of metabolically relevant inputs, highlight the rapid capacity for plasticity in medullary melanocortin circuits, and emphasize the critical importance of physiological recording conditions for electrophysiological studies pertaining to the central control of energy homeostasis. Copyright © 2015 the American Physiological Society.

  1. The effect of GABA A receptor antagonist - bicucullin - administration on the number of multiform neurons in the brain parabrachial nucleus due to pain induction of adult male rats

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    Mahsa Kamali

    2015-10-01

    Full Text Available Background and Aim:  A lot of biological investigations are aimed to find pain decreasing or relieving substances that appear in various diseases. Parabrachial nucleus plays an important role in cognitive and emotional aspects of pain. The present study was designed to evaluate the inhibitory effect of bicuculine- as a GABA A receptor antagonist- on the number of multiform neurons in Parabrachial region of adult male rats in tonic pain model. Materials and Methods: This experimental study was carried out on 40 Wistar male rats. Based on the pain induction, the animals were divided into 8 groups (n=5. Bicuculine was administrated in doses of  50, 100, and 200 ng/rat.  Using stereotaxic method, Bicuculine was administrated to the rats` brain parabrachial area. The present study utilized Formalin test as a standard method for pain stimulations. Thereafter, Gimsa staining method was applied for histological determination of multiform cells. The obtained data was analyzed using statistical testsincluding Student-t and  one-way ANOVA. Results: Our data showed no significant changes in the number of multiform cells in Parabrachial nucleus between the animals administrated by bicuculine at the dose of 50   compared  with the controls (P>0.05. Nevertheless, the number of these cells was decreased significantly in the animals administrated by bicuculine at the doses of 100 and 200   when compared to the controls (p<0.05. Conclusion:  It was found that nociceptive stimulations cause changes in the number of multiform neurons in para- brachial nucleus. Nevertheless, higher dose administration of GABA A receptor antagonist has preventive effects on neuronal dysmorphogenesis at this brain area.

  2. Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

    DEFF Research Database (Denmark)

    Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

    2010-01-01

    FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar t, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

  3. Cholecystokinin (CCK)-expressing neurons in the suprachiasmatic nucleus: innervation, light responsiveness and entrainment in CCK-deficient mice

    DEFF Research Database (Denmark)

    Hannibal, Jens; Hundahl, Christian; Fahrenkrug, Jan

    2010-01-01

    FOS, and did not express the core clock protein PER1. Accordingly, CCK-deficient mice showed normal entrainment and had similar τ, light-induced phase shift and negative masking behaviour as wild-type animals. In conclusion, CCK signalling seems not to be involved directly in light-induced resetting......, CCK-containing processes make synaptic contacts with both groups of neurons and some CCK cell bodies were innervated by VIPergic neurons. The CCK neurons received no direct input from the three major pathways to the SCN, and the CCK neurons were not light-responsive as evaluated by induction of c...

  4. Altered neuronal firing pattern of the basal ganglia nucleus plays a role in levodopa-induced dyskinesia in patients with Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xiaoyu eLi

    2015-11-01

    Full Text Available Background: Levodopa therapy alleviates the symptoms of Parkinson's disease (PD, but long-term treatment often leads to motor complications such as levodopa-induced dyskinesia (LID. Aim: To explore the neuronal activity in the basal ganglia nuclei in patients with PD and LID. Methods: Thirty patients with idiopathic PD (age, 55.1±11.0 years; disease duration, 8.7±5.6 years were enrolled between August 2006 and August 2013 at the Xuanwu Hospital, Capital Medical University, China. Their Hoehn and Yahr scores ranged from 2 to 4 and their UPDRS III scores were 28.5±5.2. Fifteen of them had severe LID (UPDRS IV scores of 6.7±1.6. Microelectrode recording was performed in the globus pallidus internus (GPi and subthalamic nucleus (STN during pallidotomy (n=12 or STN deep brain stimulation (DBS; bilateral, n=12; unilateral, n=6. The firing patterns and frequencies of various cell types were analyzed by assessing single cell interspike intervals (ISIs and the corresponding coefficient of variation (CV. Results: A total of 295 neurons were identified from the GPi (n=12 and STN (n=18. These included 26 (8.8% highly grouped discharge, 30 (10.2% low frequency firing, 78 (26.4% rapid tonic discharge, 103 (34.9% irregular activity, and 58 (19.7% tremor-related activity. There were significant differences between the two groups (P<0.05 for neurons with irregular firing, highly irregular cluster-like firing, and low-frequency firing. Conclusion: Altered neuronal activity was observed in the basal ganglia nucleus of GPi and STN, and may play important roles in the pathophysiology of PD and LID.

  5. The use of cochlear's SCAN and wireless microphones to improve speech understanding in noise with the Nucleus6® CP900 processor.

    Science.gov (United States)

    De Ceulaer, Geert; Pascoal, David; Vanpoucke, Filiep; Govaerts, Paul J

    2017-11-01

    The newest Nucleus CI processor, the CP900, has two new options to improve speech-in-noise perception: (1) use of an adaptive directional microphone (SCAN mode) and (2) wireless connection to MiniMic1 and MiniMic2 wireless remote microphones. An analysis was made of the absolute and relative benefits of these technologies in a real-world mimicking test situation. Speech perception was tested using an adaptive speech-in-noise test (sentences-in-babble noise). In session A, SRTs were measured in three conditions: (1) Clinical Map, (2) SCAN and (3) MiniMic1. Each was assessed for three distances between speakers and CI recipient: 1 m, 2 m and 3 m. In session B, the benefit of the use of MiniMic2 was compared to benefit of MiniMic1 at 3 m. A group of 13 adult CP900 recipients participated. SCAN and MiniMic1 improved performance compared to the standard microphone with a median improvement in SRT of 2.7-3.9 dB for SCAN at 1 m and 3 m, respectively, and 4.7-10.9 dB for the MiniMic1. MiniMic1 improvements were significant. MiniMic2 showed an improvement in SRT of 22.2 dB compared to 10.0 dB for MiniMic1 (3 m). Digital wireless transmission systems (i.e. MiniMic) offer a statistically and clinically significant improvement in speech perception in challenging, realistic listening conditions.

  6. Prolonged Consumption of Sucrose in a Binge-Like Manner, Alters the Morphology of Medium Spiny Neurons in the Nucleus Accumbens Shell.

    Directory of Open Access Journals (Sweden)

    Paul M Klenowski

    2016-03-01

    Full Text Available The modern diet has become highly sweetened, resulting in unprecedented levels of sugar consumption, particularly among adolescents. While chronic long-term sugar intake is known to contribute to the development of metabolic disorders including obesity and type II diabetes, little is known regarding the direct consequences of long-term, binge-like sugar consumption on the brain. Because sugar can cause the release of dopamine in the nucleus accumbens (NAc similarly to drugs of abuse, we investigated changes in the morphology of neurons in this brain region following short- (4 weeks and long-term (12 weeks binge-like sucrose consumption using an intermittent two-bottle choice paradigm. We used Golgi-Cox staining to impregnate medium spiny neurons (MSNs from the NAc core and shell of short- and long-term sucrose consuming rats and compared these to age matched water controls. We show that prolonged binge-like sucrose consumption significantly decreased the total dendritic length of NAc shell MSNs compared to age-matched control rats. We also found that the restructuring of these neurons resulted primarily from reduced distal dendritic complexity. Conversely, we observed increased spine densities at the distal branch orders of NAc shell MSNs from long-term sucrose consuming rats. Combined, these results highlight the neuronal effects of prolonged binge-like intake of sucrose on NAc shell MSN morphology.

  7. Neuronal responses to tactile stimuli and tactile sensations evoked by microstimulation in the human thalamic principal somatic sensory nucleus (ventral caudal).

    Science.gov (United States)

    Schmid, Anne-Christine; Chien, Jui-Hong; Greenspan, Joel D; Garonzik, Ira; Weiss, Nirit; Ohara, Shinji; Lenz, Frederick Arthur

    2016-06-01

    The normal organization and plasticity of the cutaneous core of the thalamic principal somatosensory nucleus (ventral caudal, Vc) have been studied by single-neuron recordings and microstimulation in patients undergoing awake stereotactic operations for essential tremor (ET) without apparent somatic sensory abnormality and in patients with dystonia or chronic pain secondary to major nervous system injury. In patients with ET, most Vc neurons responded to one of the four stimuli, each of which optimally activates one mechanoreceptor type. Sensations evoked by microstimulation were similar to those evoked by the optimal stimulus only among rapidly adapting neurons. In patients with ET, Vc was highly segmented somatotopically, and vibration, movement, pressure, and sharp sensations were usually evoked by microstimulation at separate sites in Vc. In patients with conditions including spinal cord transection, amputation, or dystonia, RFs were mismatched with projected fields more commonly than in patients with ET. The representation of the border of the anesthetic area (e.g., stump) or of the dystonic limb was much larger than that of the same part of the body in patients with ET. This review describes the organization and reorganization of human Vc neuronal activity in nervous system injury and dystonia and then proposes basic mechanisms. Copyright © 2016 the American Physiological Society.

  8. Consistency and diversity of spike dynamics in the neurons of bed nucleus of stria terminalis of the rat: a dynamic clamp study.

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    Attila Szücs

    Full Text Available Neurons display a high degree of variability and diversity in the expression and regulation of their voltage-dependent ionic channels. Under low level of synaptic background a number of physiologically distinct cell types can be identified in most brain areas that display different responses to standard forms of intracellular current stimulation. Nevertheless, it is not well understood how biophysically different neurons process synaptic inputs in natural conditions, i.e., when experiencing intense synaptic bombardment in vivo. While distinct cell types might process synaptic inputs into different patterns of action potentials representing specific "motifs" of network activity, standard methods of electrophysiology are not well suited to resolve such questions. In the current paper we performed dynamic clamp experiments with simulated synaptic inputs that were presented to three types of neurons in the juxtacapsular bed nucleus of stria terminalis (jcBNST of the rat. Our analysis on the temporal structure of firing showed that the three types of jcBNST neurons did not produce qualitatively different spike responses under identical patterns of input. However, we observed consistent, cell type dependent variations in the fine structure of firing, at the level of single spikes. At the millisecond resolution structure of firing we found high degree of diversity across the entire spectrum of neurons irrespective of their type. Additionally, we identified a new cell type with intrinsic oscillatory properties that produced a rhythmic and regular firing under synaptic stimulation that distinguishes it from the previously described jcBNST cell types. Our findings suggest a sophisticated, cell type dependent regulation of spike dynamics of neurons when experiencing a complex synaptic background. The high degree of their dynamical diversity has implications to their cooperative dynamics and synchronization.

  9. Targeted deletion of neurokinin-1 receptor expressing nucleus tractus solitarii neurons precludes somatosensory depression of arterial baroreceptor-heart rate reflex.

    Science.gov (United States)

    Potts, J T; Fong, A Y; Anguelov, P I; Lee, S; McGovern, D; Grias, I

    2007-03-30

    Neurokinin-1 receptor (NK1-R) expressing neurons are densely distributed throughout the nucleus tractus solitarii (NTS). However, their fundamental role in arterial baroreflex function remains debated. Previously, our group has shown that activation of contraction-sensitive somatic afferents evoke substance P (SP) release in the NTS and resets the arterial baroreflex via activation of a GABAergic NTS circuit. Based on these findings, we hypothesized that modulation of arterial baroreflex function by somatic afferents is mediated by NK1-R dependent inhibition of barosensitive NTS circuits. In the present study, SP-conjugated saporin toxin (SP-SAP) was used to ablate NK1-R expressing NTS neurons. Contraction-sensitive somatic afferents were activated by electrically-evoked muscle contraction and the arterial baroreceptor-heart rate reflex was assessed by constructing reflex curves using a decerebrate, arterially-perfused preparation. Baseline baroreflex sensitivity was significantly attenuated in SP-SAP-treated rats compared with control rats receiving either unconjugated SAP or vehicle. Muscle contraction significantly attenuated baroslope in SAP and vehicle-treated animals and shifted the baroreflex curves to higher systemic pressure. In contrast, somatic afferent stimulation failed to alter baroslope or shift the baroreflex curves in SP-SAP-treated animals. Moreover, when reflex sensitivity was partially restored in SP-SAP animals, somatic stimulation failed to attenuate baroreflex bradycardia. In contrast, SP-SAP and somatic stimulation failed to blunt the reflex bradycardia evoked by the peripheral chemoreflex. Immunohistochemistry revealed that pretreatment with SP-SAP significantly reduced the number of NK1-R expressing neurons in the caudal NTS, while sparing NK1-R expressing neurons rostral to the injection site. This was accompanied by a significant reduction in the number of glutamic acid decarboxylase (GAD67) expressing neurons at equivalent levels of the

  10. Spectral composition of concurrent noise affects neuronal sensitivity to interaural time differences of tones in the dorsal nucleus of the lateral lemniscus.

    Science.gov (United States)

    Siveke, Ida; Leibold, Christian; Grothe, Benedikt

    2007-11-01

    We are regularly exposed to several concurrent sounds, producing a mixture of binaural cues. The neuronal mechanisms underlying the localization of concurrent sounds are not well understood. The major binaural cues for localizing low-frequency sounds in the horizontal plane are interaural time differences (ITDs). Auditory brain stem neurons encode ITDs by firing maximally in response to "favorable" ITDs and weakly or not at all in response to "unfavorable" ITDs. We recorded from ITD-sensitive neurons in the dorsal nucleus of the lateral lemniscus (DNLL) while presenting pure tones at different ITDs embedded in noise. We found that increasing levels of concurrent white noise suppressed the maximal response rate to tones with favorable ITDs and slightly enhanced the response rate to tones with unfavorable ITDs. Nevertheless, most of the neurons maintained ITD sensitivity to tones even for noise intensities equal to that of the tone. Using concurrent noise with a spectral composition in which the neuron's excitatory frequencies are omitted reduced the maximal response similar to that obtained with concurrent white noise. This finding indicates that the decrease of the maximal rate is mediated by suppressive cross-frequency interactions, which we also observed during monaural stimulation with additional white noise. In contrast, the enhancement of the firing rate to tones at unfavorable ITD might be due to early binaural interactions (e.g., at the level of the superior olive). A simple simulation corroborates this interpretation. Taken together, these findings suggest that the spectral composition of a concurrent sound strongly influences the spatial processing of ITD-sensitive DNLL neurons.

  11. Anatomical evidence for direct fiber projections from the cerebellar nucleus interpositus to rubrospinal neurons. A quantitative EM study in the rat combining anterograde and retrograde intra-axonal tracing methods

    International Nuclear Information System (INIS)

    Dekker, J.J.

    1981-01-01

    A quantitative electron microscopic (EM) study combining the anterograde intra-axonal transport of radioactive amino acids and the retrograde intra-axonal transport of the enzyme horseradish peroxidase (HRP) was performed in the magnocellular red nucleus of the rat to obtain anatomical evidence as to whether there is a direct projection from the cerebellar nucleus interpositus to the cells in the red nucleus that give rise to the rubrospinal tract. Large asymmetrical synaptic terminals were radioactively labeled in the magnocellular red nucleus following injections of [ 3 H]leucine into the cerebellar nucleus interpositus. In these same animals, the postsynaptic target neurons were labeled with HRP granules after injection of this substance in the rubrospinal tract. A quantitative analysis showed that more than 85% of the large and giant neurons in the magnocellular red nucleus were labeled with HRP granules and also received synaptic contacts from radioactively-labeled terminals. Thus, it can be concluded that in the rat, afferents from the cerebellar nucleus interpositus establish asymmetrical synaptic contacts with large and giant rubrospinal neurons, thus confirming and extending the previous physiological evidence of such direct monosynaptic connections. (Auth.)

  12. Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

    Directory of Open Access Journals (Sweden)

    Xianglong eZhu

    2016-04-01

    Full Text Available While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running. The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control.

  13. Activation of Hypocretin-1/Orexin-A Neurons Projecting to the Bed Nucleus of the Stria Terminalis and Paraventricular Nucleus Is Critical for Reinstatement of Alcohol Seeking by Neuropeptide S.

    Science.gov (United States)

    Ubaldi, Massimo; Giordano, Antonio; Severi, Ilenia; Li, Hongwu; Kallupi, Marsida; de Guglielmo, Giordano; Ruggeri, Barbara; Stopponi, Serena; Ciccocioppo, Roberto; Cannella, Nazzareno

    2016-03-15

    Environmental conditioning is a major trigger for relapse in abstinent addicts. We showed that activation of the neuropeptide S (NPS) system exacerbates reinstatement vulnerability to cocaine and alcohol via stimulation of the hypocretin-1/orexin-A (Hcrt-1/Ox-A) system. Combining pharmacologic manipulations with immunohistochemistry techniques, we sought to determine how NPS and Hcrt-1/Ox-A systems interact to modulate reinstatement of alcohol seeking in rats. Intrahypothalamic injection of NPS facilitated discriminative cue-induced reinstatement of alcohol seeking. This effect was blocked by the selective Hcrt-1/Ox-A antagonist SB334867 microinjected into the hypothalamic paraventricular nucleus (PVN) or into the bed nucleus of the stria terminalis (BNST) but not into the ventral tegmental area or the locus coeruleus. Combining double labeling and confocal microscopy analyses, we found that NPS-containing axons are in close apposition to hypothalamic Hcrt-1/Ox-A positive neurons, a significant proportion of which express NPS receptors, suggesting a direct interaction between the two systems. Retrograde tracing experiments showed that intra-PVN or intra-BNST red fluorobead unilateral injection labeled bilaterally Hcrt-1/Ox-A somata, suggesting that NPS could recruit two distinct neuronal pathways. Confirming this assumption, intra-BNST or PVN Hcrt-1/Ox-A injection enhanced alcohol seeking similarly to hypothalamic NPS injection but to a lesser degree. Results suggest that the Hcrt-1/Ox-A neurocircuitry mediating the facilitation of cue-induced reinstatement by NPS involves structures critically involved in stress regulation such as the PVN and the BNST. These findings open to the tempting hypothesis of a role of the NPS system in modulating the interactions between stress and environmental conditioning factors in drug relapse. Copyright © 2016. Published by Elsevier Inc.

  14. Physiology of spontaneous [Ca2+](i) oscillations in the isolated vasopressin and oxytocin neurones of the rat supraoptic nucleus

    Czech Academy of Sciences Publication Activity Database

    Kortus, Štěpán; Srinivasan, Ch.; Forostyak, O.; Ueta, Y.; Syková, E.; Chvátal, A.; Zápotocký, Martin; Verkhratsky, A.; Dayanithi, G.

    2016-01-01

    Roč. 59, č. 6 (2016), s. 280-288 ISSN 0143-4160 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : magnocellular neurosecretory cells * supraoptic nucleus * vasopressin * oxytocin * transgenic rats * Ca2+ oscillations Subject RIV: FH - Neurology Impact factor: 3.707, year: 2016

  15. Golgi-type I and Golgi-type II neurons in the ventral anterior thalamic nucleus of the adult human: morphological features and quantitative analysis.

    Science.gov (United States)

    Al-Hussain Bani Hani, Saleh M; El-Dwairi, Qasim A; Bataineh, Ziad M; Al-Haidari, Mohammad S; Al-Alami, Jamil

    2008-05-01

    The morphological and quantitative features of neurons in the adult human ventral anterior thalamic nucleus were studied in Golgi preparations. Two neuronal types were found and their quantitative features were studied. Golgi-type I neurons were medium to large cells with dense dendritic trees and dendritic protrusions and short hair-like appendages. They have somatic mean diameter of 30.8 microm (+/-9.4, n = 85). They have an average 100.3 dendritic branches, 48.97 dendritic branching points, and 58.85 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 3.1 microm (+/-1, n = 80), 1.85 microm (+/-0.8, n = 145), and 1.5 microm (+/-0.4, n = 160), respectively. Golgi-type II neurons were small to medium cells with few sparsely branching dendrites and dendritic stalked appendages with or without terminal swellings. They have somatic mean diameters of 22.2 microm (+/-5.8, n = 120). They have an average 33.76 dendritic branches, 16.49 dendritic branching points, and 21.97 dendritic tips. The mean diameters of their primary, secondary, and tertiary dendrites were 1.6 microm (+/-0.86, n = 70), 1.15 microm (+/-0.55, n = 118), and 1 microm (+/-0.70, n = 95), respectively. These quantitative data may form the basis for further quantitative studies involving aging or some degenerative diseases that may affect cell bodies and/or dendritic trees of the Golgi-type I and/or Golgi-type II thalamic neurons.

  16. High glucose increases action potential firing of catecholamine neurons in the nucleus of the solitary tract by increasing spontaneous glutamate inputs.

    Science.gov (United States)

    Roberts, Brandon L; Zhu, Mingyan; Zhao, Huan; Dillon, Crystal; Appleyard, Suzanne M

    2017-09-01

    Glucose is a crucial substrate essential for cell survival and function. Changes in glucose levels impact neuronal activity and glucose deprivation increases feeding. Several brain regions have been shown to respond to glucoprivation, including the nucleus of the solitary tract (NTS) in the brain stem. The NTS is the primary site in the brain that receives visceral afferent information from the gastrointestinal tract. The catecholaminergic (CA) subpopulation within the NTS modulates many homeostatic functions including cardiovascular reflexes, respiration, food intake, arousal, and stress. However, it is not known if they respond to changes in glucose. Here we determined whether NTS-CA neurons respond to changes in glucose concentration and the mechanism involved. We found that decreasing glucose concentrations from 5 mM to 2 mM to 1 mM, significantly decreased action potential firing in a cell-attached preparation, whereas increasing it back to 5 mM increased the firing rate. This effect was dependent on glutamate release from afferent terminals and required presynaptic 5-HT 3 Rs. Decreasing the glucose concentration also decreased both basal and 5-HT 3 R agonist-induced increase in the frequency of spontaneous glutamate inputs onto NTS-CA neurons. Low glucose also blunted 5-HT-induced inward currents in nodose ganglia neurons, which are the cell bodies of vagal afferents. The effect of low glucose in both nodose ganglia cells and in NTS slices was mimicked by the glucokinase inhibitor glucosamine. This study suggests that NTS-CA neurons are glucosensing through a presynaptic mechanism that is dependent on vagal glutamate release, 5-HT 3 R activity, and glucokinase. Copyright © 2017 the American Physiological Society.

  17. Orexinergic fibers are in contact with Kölliker-Fuse nucleus neurons projecting to the respiration-related nuclei in the medulla oblongata and spinal cord of the rat.

    Science.gov (United States)

    Yokota, Shigefumi; Oka, Tatsuro; Asano, Hirohiko; Yasui, Yukihiko

    2016-10-01

    The neural pathways underlying the respiratory variation dependent on vigilance states remain unsettled. In the present study, we examined the orexinergic innervation of Kölliker-Fuse nucleus (KFN) neurons sending their axons to the rostral ventral respiratory group (rVRG) and phrenic nucleus (PhN) as well as to the hypoglossal nucleus (HGN) by using a combined retrograde tracing and immunohistochemistry. After injection of cholera toxin B subunit (CTb) into the KFN, CTb-labeled neurons that are also immunoreactive for orexin (ORX) were found prominently in the perifornical and medial regions and additionally in the lateral region of the hypothalamic ORX field. After injection of fluorogold (FG) into the rVRG, PhN or HGN, we found an overlapping distribution of ORX-immunoreactive axon terminals and FG-labeled neurons in the KFN. Within the neuropil of the KFN, asymmetrical synaptic contacts were made between these terminals and neurons. We further demonstrated that many neurons labeled with FG injected into the rVRG, PhN, or HGN are immunoreactive for ORX receptor 2. Present data suggest that rVRG-, PhN- and HGN-projecting KFN neurons may be under the excitatory influence of the ORXergic neurons for the state-dependent regulation of respiration. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Chronic intermittent hypoxia impairs heart rate responses to AMPA and NMDA and induces loss of glutamate receptor neurons in nucleus ambiguous of F344 rats.

    Science.gov (United States)

    Yan, Binbin; Li, Lihua; Harden, Scott W; Gozal, David; Lin, Ying; Wead, William B; Wurster, Robert D; Cheng, Zixi Jack

    2009-02-01

    Chronic intermittent hypoxia (CIH), as occurs in sleep apnea, impairs baroreflex-mediated reductions in heart rate (HR) and enhances HR responses to electrical stimulation of vagal efferent. We tested the hypotheses that HR responses to activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-D-aspartate (NMDA) receptors in the nucleus ambiguous (NA) are reduced in CIH-exposed rats and that this impairment is associated with degeneration of glutamate receptor (GluR)-immunoreactive NA neurons. Fischer 344 rats (3-4 mo) were exposed to room air (RA) or CIH for 35-50 days (n = 18/group). At the end of the exposures, AMPA (4 pmol, 20 nl) and NMDA (80 pmol, 20 nl) were microinjected into the same location of the left NA (-200 microm to +200 microm relative to caudal end of area postrema; n = 6/group), and HR and arterial blood pressure responses were measured. In addition, brain stem sections at the level of -800, -400, 0, +400, and +800 microm relative to obex were processed for AMPA and NMDA receptor immunohistochemistry. The number of NA neurons expressing AMPA receptors and NMDA receptors (NMDARs) was quantified. Compared with RA, we found that after CIH 1) HR responses to microinjection of AMPA into the left NA were reduced (RA -290 +/- 30 vs. CIH -227 +/- 15 beats/min, P neurons expressing GluRs contributes to impaired baroreflex control of HR in rats exposed to CIH.

  19. The Neuronal Transition Probability (NTP) Model for the Dynamic Progression of Non-REM Sleep EEG: The Role of the Suprachiasmatic Nucleus

    CERN Document Server

    Merica, H

    2011-01-01

    Little attention has gone into linking to its neuronal substrates the dynamic structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time-course power in all frequency bands across an entire episode. Using the spectral power time-courses in the sleep electroencephalogram (EEG), we showed in the typical first episode, several moves towards-and-away from deep sleep, each having an identical pattern linking the major frequency bands beta, sigma and delta. The neuronal transition probability model (NTP) - in fitting the data well - successfully explained the pattern as resulting from stochastic transitions of the firing-rates of the thalamically-projecting brainstem-activating neurons, alternating between two steady dynamic-states (towards-and-away from deep sleep) each initiated by a so-far unidentified flip-flop. The aims here are to identify this flip-flop and to demonstrate that the model fits well all NREM episodes, not just the first. Using published data on suprachiasmatic nucleus (SCN...

  20. Bilateral LMAN lesions cancel differences in HVC neuronal recruitment induced by unilateral syringeal denervation. Lateral magnocellular nucleus of the anterior neostriatum.

    Science.gov (United States)

    Wilbrecht, L; Petersen, T; Nottebohm, F

    2002-12-01

    Twenty-six-day-old male zebra finches received (1) unilateral section of their tracheosyringeal nerve, (2) bilateral lesions of the lateral magnocellular nucleus of the anterior neostriatum (LMAN), and (3) both operations. All birds were kept with an adult, singing male as a tutor until day 65. Tracheo-syringeal nerve-cut birds were able to imitate this model, but LMAN-lesioned birds were not. Bromodeoxyuridine, a marker of cell division, was injected intramuscularly during post-hatching days 61-65 and all birds were killed at 91 days of age. The number of bromodeoxyuridine+ neurons in the high vocal center of the tracheosyringeal-cut birds was twice as high in the intact as in the nerve cut side. This asymmetry disappeared when nerve section was combined with bilateral LMAN lesions. The latter operation, by itself, had no effect on new neuron counts. We suggest that the single nerve cut produced a hemispheric asymmetry in learning, reflected in new neuron recruitment, which disappeared when LMAN lesions blocked learning.

  1. Nucleus Accumbens Dopamine D1-Receptor-Expressing Neurons Control the Acquisition of Sign-Tracking to Conditioned Cues in Mice

    Directory of Open Access Journals (Sweden)

    Tom Macpherson

    2018-06-01

    Full Text Available Following repeated pairings, the reinforcing and motivational properties (incentive salience of a reward can be transferred onto an environmental stimulus which can then elicit conditioned responses, including Pavlovian approach behavior to the stimulus (a sign-tracking response. In rodents, acquisition of sign-tracking in autoshaping paradigms is sensitive to lesions and dopamine D1 receptor antagonism of the nucleus accumbens (NAc of the ventral striatum. However, currently, the possible roles of dorsal striatal subregions, as well as of the two major striatal neuron types, dopamine D1-/D2-expressing medium spiny neurons (MSNs, in controlling the development of conditioned responses is still unclear and warrants further study. Here, for the first time, we used a transgenic mouse line combined with striatal subregion-specific AAV virus injections to separately express tetanus toxin in D1-/D2- MSNs in the NAc, dorsomedial striatum, and dorsolateral striatum, to permanently block neurotransmission in these neurons during acquisition of an autoshaping task. Neurotransmission blocking of NAc D1-MSNs inhibited the acquisition of sign-tracking responses when the initial conditioned response for each conditioned stimulus presentation was examined, confirming our initial hypothesis. These findings suggest that activity in NAc D1-MSNs contributes to the attribution of incentive salience to conditioned stimuli.

  2. Effect of morphine-induced antinociception is altered by AF64A-induced lesions on cholinergic neurons in rat nucleus raphe magnus.

    Science.gov (United States)

    Abe, Kenji; Ishida, Kota; Kato, Masatoshi; Shigenaga, Toshiro; Taguchi, Kyoji; Miyatake, Tadashi

    2002-11-01

    To examine the role of cholinergic neurons in the nucleus raphe magnus (NRM) in noxious heat stimulation and in the effects of morphine-induced antinociception by rats. After the cholinergic neuron selective toxin, AF64A, was microinjected into the NRM, we examined changes in the antinociceptive threshold and effects of morphine (5 mg/kg, ip) using the hot-plate (HP) and tail-flick (TF) tests. Systemic administration of morphine inhibited HP and TF responses in control rats. Microinjection of AF64A (2 nmol/site) into the NRM significantly decreased the threshold of HP response after 14 d, whereas the TF response was not affected. Morphine-induced antinociception was significantly attenuated in rats administered AF64A. Extracellular acetylcholine was attenuated after 14 d to below detectable levels in rats given AF64A. Naloxone (1 microg/site) microinjected into control rat NRM also antagonized the antinociceptive effect of systemic morphine. These findings suggest that cholinergic neuron activation in the NRM modulates the antinociceptive effect of morphine simultaneously with the opiate system.

  3. Remote programming of cochlear implants: a telecommunications model.

    Science.gov (United States)

    McElveen, John T; Blackburn, Erin L; Green, J Douglas; McLear, Patrick W; Thimsen, Donald J; Wilson, Blake S

    2010-09-01

    Evaluate the effectiveness of remote programming for cochlear implants. Retrospective review of the cochlear implant performance for patients who had undergone mapping and programming of their cochlear implant via remote connection through the Internet. Postoperative Hearing in Noise Test and Consonant/Nucleus/Consonant word scores for 7 patients who had undergone remote mapping and programming of their cochlear implant were compared with the mean scores of 7 patients who had been programmed by the same audiologist over a 12-month period. Times required for remote and direct programming were also compared. The quality of the Internet connection was assessed using standardized measures. Remote programming was performed via a virtual private network with a separate software program used for video and audio linkage. All 7 patients were programmed successfully via remote connectivity. No untoward patient experiences were encountered. No statistically significant differences could be found in comparing postoperative Hearing in Noise Test and Consonant/Nucleus/Consonant word scores for patients who had undergone remote programming versus a similar group of patients who had their cochlear implant programmed directly. Remote programming did not require a significantly longer programming time for the audiologist with these 7 patients. Remote programming of a cochlear implant can be performed safely without any deterioration in the quality of the programming. This ability to remotely program cochlear implant patients gives the potential to extend cochlear implantation to underserved areas in the United States and elsewhere.

  4. Neuron-specific specificity protein 4 bigenomically regulates the transcription of all mitochondria- and nucleus-encoded cytochrome c oxidase subunit genes in neurons.

    Science.gov (United States)

    Johar, Kaid; Priya, Anusha; Dhar, Shilpa; Liu, Qiuli; Wong-Riley, Margaret T T

    2013-11-01

    Neurons are highly dependent on oxidative metabolism for their energy supply, and cytochrome c oxidase (COX) is a key energy-generating enzyme in the mitochondria. A unique feature of COX is that it is one of only four proteins in mammalian cells that are bigenomically regulated. Of its thirteen subunits, three are encoded in the mitochondrial genome and ten are nuclear-encoded on nine different chromosomes. The mechanism of regulating this multisubunit, bigenomic enzyme poses a distinct challenge. In recent years, we found that nuclear respiratory factors 1 and 2 (NRF-1 and NRF-2) mediate such bigenomic coordination. The latest candidate is the specificity factor (Sp) family of proteins. In N2a cells, we found that Sp1 regulates all 13 COX subunits. However, we discovered recently that in primary neurons, it is Sp4 and not Sp1 that regulates some of the key glutamatergic receptor subunit genes. The question naturally arises as to the role of Sp4 in regulating COX in primary neurons. The present study utilized multiple approaches, including chromatin immunoprecipitation, promoter mutational analysis, knockdown and over-expression of Sp4, as well as functional assays to document that Sp4 indeed functionally regulate all 13 subunits of COX as well as mitochondrial transcription factors A and B. The present study discovered that among the specificity family of transcription factors, it is the less known neuron-specific Sp4 that regulates the expression of all 13 subunits of mitochondrial cytochrome c oxidase (COX) enzyme in primary neurons. Sp4 also regulates the three mitochondrial transcription factors (TFAM, TFB1M, and TFB2M) and a COX assembly protein SURF-1 in primary neurons. © 2013 International Society for Neurochemistry.

  5. S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

    Science.gov (United States)

    Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

    2018-01-01

    Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to

  6. Cochlear Implant

    Directory of Open Access Journals (Sweden)

    Mehrnaz Karimi

    1992-04-01

    Full Text Available People with profound hearing loss are not able to use some kinds of conventional amplifiers due to the nature of their loss . In these people, hearing sense is stimulated only when the auditory nerve is activated via electrical stimulation. This stimulation is possible through cochlear implant. In fact, for the deaf people who have good mental health and can not use surgical and medical treatment and also can not benefit from air and bone conduction hearing aids, this device is used if they have normal central auditory system. The basic parts of the device included: Microphone, speech processor, transmitter, stimulator and receiver, and electrode array.

  7. Neuronal degeneration induced by status epilepticus in the thalami reuniens nucleus of immature rats. Are calcium binding proteins neuroprotective?

    Czech Academy of Sciences Publication Activity Database

    Druga, Rastislav; Kubová, Hana; Mareš, Pavel

    2006-01-01

    Roč. 47, č. S4 (2006), s. 302-302 ISSN 0013-9580. [Annual Meeting of the American Epilepsy Society and Canadian League against Epilepsy. 01.12.2006-05.12.2006, San Diego, CA] R&D Projects: GA ČR(CZ) GA304/04/0464 Institutional research plan: CEZ:AV0Z50110509 Keywords : pilocarpine * neurodegeneration * nucleus reuniens Subject RIV: ED - Physiology

  8. Spread of cochlear excitation during stimulation with pulsed infrared radiation: inferior colliculus measurements

    Science.gov (United States)

    Richter, C.-P.; Rajguru, S. M.; Matic, A. I.; Moreno, E. L.; Fishman, A. J.; Robinson, A. M.; Suh, E.; Walsh, J. T., Jr.

    2011-10-01

    Infrared neural stimulation (INS) has received considerable attention over the last few years. It provides an alternative method to artificially stimulate neurons without electrical current or the introduction of exogenous chromophores. One of the primary benefits of INS could be the improved spatial selectivity when compared with electrical stimulation. In the present study, we have evaluated the spatial selectivity of INS in the acutely damaged cochlea of guinea pigs and compared it to stimulation with acoustic tone pips in normal-hearing animals. The radiation was delivered via a 200 µm diameter optical fiber, which was inserted through a cochleostomy into the scala tympani of the basal cochlear turn. The stimulated section along the cochlear spiral ganglion was estimated from the neural responses recorded from the central nucleus of the inferior colliculus (ICC). ICC responses were recorded in response to cochlear INS using a multichannel penetrating electrode array. Spatial tuning curves (STCs) were constructed from the responses. For INS, approximately 55% of the activation profiles showed a single maximum, ~22% had two maxima and ~13% had multiple maxima. The remaining 10% of the profiles occurred at the limits of the electrode array and could not be classified. The majority of ICC STCs indicated that the spread of activation evoked by optical stimuli is comparable to that produced by acoustic tone pips.

  9. Lesions of cholinergic pedunculopontine tegmental nucleus neurons fail to affect cocaine or heroin self-administration or conditioned place preference in rats.

    Directory of Open Access Journals (Sweden)

    Stephan Steidl

    Full Text Available Cholinergic input to the ventral tegmental area (VTA is known to contribute to reward. Although it is known that the pedunculopontine tegmental nucleus (PPTg provides an important source of excitatory input to the dopamine system, the specific role of PPTg cholinergic input to the VTA in cocaine reward has not been previously determined. We used a diphtheria toxin conjugated to urotensin-II (Dtx::UII, the endogenous ligand for urotensin-II receptors expressed by PPTg cholinergic but not glutamatergic or GABAergic cells, to lesion cholinergic PPTg neurons. Dtx::UII toxin infusion resulted in the loss of 95.78 (±0.65% of PPTg cholinergic cells but did not significantly alter either cocaine or heroin self-administration or the development of cocaine or heroin conditioned place preferences. Thus, cholinergic cells originating in PPTg do not appear to be critical for the rewarding effects of cocaine or of heroin.

  10. Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex

    NARCIS (Netherlands)

    Ishunina, T. A.; Swaab, D. F.

    1999-01-01

    The hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei consist of arginine vasopressin (AVP)- and oxytocin (OT)-synthesizing neurons that send projections to the neurohypophysis, whereas the PVN also projects to other brain areas. A growing body of evidence in animals suggests the

  11. The lateral paragigantocellular nucleus modulates parasympathetic cardiac neurons: a mechanism for rapid eye movement sleep-dependent changes in heart rate.

    Science.gov (United States)

    Dergacheva, Olga; Wang, Xin; Lovett-Barr, Mary R; Jameson, Heather; Mendelowitz, David

    2010-08-01

    Rapid eye movement (REM) sleep is generally associated with a withdrawal of parasympathetic activity and heart rate increases; however, episodic vagally mediated heart rate decelerations also occur during REM sleep. This alternating pattern of autonomic activation provides a physiological basis for REM sleep-induced cardiac arrhythmias. Medullary neurons within the lateral paragigantocellular nucleus (LPGi) are thought to be active after REM sleep recovery and play a role in REM sleep control. In proximity to the LPGi are parasympathetic cardiac vagal neurons (CVNs) within the nucleus ambiguus (NA), which are critical for controlling heart rate. This study examined brain stem pathways that may mediate REM sleep-related reductions in parasympathetic cardiac activity. Electrical stimulation of the LPGi evoked inhibitory GABAergic postsynaptic currents in CVNs in an in vitro brain stem slice preparation in rats. Because brain stem cholinergic mechanisms are involved in REM sleep regulation, we also studied the role of nicotinic neurotransmission in modulation of GABAergic pathway from the LGPi to CVNs. Application of nicotine diminished the GABAergic responses evoked by electrical stimulation. This inhibitory effect of nicotine was prevented by the alpha7 nicotinic receptor antagonist alpha-bungarotoxin. Moreover, hypoxia/hypercapnia (H/H) diminished LPGi-evoked GABAergic current in CVNs, and this inhibitory effect was also prevented by alpha-bungarotoxin. In conclusion, stimulation of the LPGi evokes an inhibitory pathway to CVNs, which may constitute a mechanism for the reduced parasympathetic cardiac activity and increase in heart rate during REM sleep. Inhibition of this pathway by nicotinic receptor activation and H/H may play a role in REM sleep-related and apnea-associated bradyarrhythmias.

  12. INCREASE IN DOPAMINE RELEASE FROM THE NUCLEUS-ACCUMBENS IN RESPONSE TO FEEDING - A MODEL TO STUDY INTERACTIONS BETWEEN DRUGS AND NATURALLY ACTIVATED DOPAMINERGIC-NEURONS IN THE RAT-BRAIN

    NARCIS (Netherlands)

    WESTERINK, BHC; TEISMAN, A; DEVRIES, JB

    The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a

  13. ApoE epsilon4 genotype is accompanied by lower metabolic activity in nucleus basalis of Meynert neurons in Alzheimer patients and controls as indicated by the size of the Golgi apparatus

    NARCIS (Netherlands)

    Dubelaar, E. J. G.; Verwer, R. W. H.; Hofman, M. A.; van Heerikhuize, J. J.; Ravid, R.; Swaab, D. F.

    2004-01-01

    We previously found apolipoprotein (apoE) epsilon4-dependent lower metabolic activity in nucleus basalis of Meynert (NBM) neurons in Alzheimer disease (AD). In the present study we examined the metabolic activity in the NBM of 39 mentally intact control subjects with different APOE genotype. The

  14. THC alters alters morphology of neurons in medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens and alters the ability of later experience to promote structural plasticity.

    Science.gov (United States)

    Kolb, Bryan; Li, Yilin; Robinson, Terry; Parker, Linda A

    2018-03-01

    Psychoactive drugs have the ability to alter the morphology of neuronal dendrites and spines and to influence later experience-dependent structural plasticity. If rats are given repeated injections of psychomotor stimulants (amphetamine, cocaine, nicotine) prior to being placed in complex environments, the drug experience interferes with the ability of the environment to increase dendritic arborization and spine density. Repeated exposure to Delta 9-Tetrahydrocannabinol (THC) changes the morphology of dendrites in medial prefrontal cortex (mPFC) and nucleus accumbens (NAcc). To determine if drugs other than psychomotor stimulants will also interfere with later experience-dependent structural plasticity we gave Long-Evans rats THC (0.5 mg/kg) or saline for 11 days before placing them in complex environments or standard laboratory caging for 90 days. Brains were subsequently processed for Golgi-Cox staining and analysis of dendritic morphology and spine density mPFC, orbital frontal cortex (OFC), and NAcc. THC altered both dendritic arborization and spine density in all three regions, and, like psychomotor stimulants, THC influenced the effect of later experience in complex environments to shape the structure of neurons in these three regions. We conclude that THC may therefore contribute to persistent behavioral and cognitive deficits associated with prolonged use of the drug. © 2017 Wiley Periodicals, Inc.

  15. Maresin 1 Inhibits TRPV1 in Temporomandibular Joint-Related Trigeminal Nociceptive Neurons and TMJ Inflammation-Induced Synaptic Plasticity in the Trigeminal Nucleus

    Directory of Open Access Journals (Sweden)

    Chul-Kyu Park

    2015-01-01

    Full Text Available In the trigeminal system, disruption of acute resolution processing may lead to uncontrolled inflammation and chronic pain associated with the temporomandibular joint (TMJ. Currently, there are no effective treatments for TMJ pain. Recently, it has been recognized that maresin 1, a newly identified macrophage-derived mediator of inflammation resolution, is a potent analgesic for somatic inflammatory pain without noticeable side effects in mice and a potent endogenous inhibitor of transient receptor potential vanilloid 1 (TRPV1 in the somatic system. However, the molecular mechanisms underlying the analgesic actions of maresin 1 on TMJ pain are unclear in the trigeminal system. Here, by performing TMJ injection of a retrograde labeling tracer DiI (a fluorescent dye, I showed that maresin 1 potently inhibits capsaicin-induced TRPV1 currents and neuronal activity via Gαi-coupled G-protein coupled receptors in DiI-labeled trigeminal nociceptive neurons. Further, maresin 1 blocked TRPV1 agonist-evoked increases in spontaneous excitatory postsynaptic current frequency and abolished TMJ inflammation-induced synaptic plasticity in the trigeminal nucleus. These results demonstrate the potent actions of maresin 1 in regulating TRPV1 in the trigeminal system. Thus, maresin 1 may serve as a novel endogenous inhibitor for treating TMJ-inflammatory pain in the orofacial region.

  16. Co-localization of hypocretin-1 and leucine-enkephalin in hypothalamic neurons projecting to the nucleus of the solitary tract and their effect on arterial pressure.

    Science.gov (United States)

    Ciriello, J; Caverson, M M; McMurray, J C; Bruckschwaiger, E B

    2013-10-10

    Experiments were done to investigate whether hypothalamic hypocretin-1 (hcrt-1; orexin-A) neurons that sent axonal projections to cardiovascular responsive sites in the nucleus of the solitary tract (NTS) co-expressed leucine-enkephalin (L-Enk), and to determine the effects of co-administration of hcrt-1 and D-Ala2,D-Leu5-Enkephalin (DADL) into NTS on mean arterial pressure (MAP) and heart rate. In the first series, in the Wistar rat the retrograde tract-tracer fluorogold (FG) was microinjected (50nl) into caudal NTS sites at which L-glutamate (0.25 M; 10 nl) elicited decreases in MAP and where fibers hcrt-1 immunoreactive fibers were observed that also contained L-Enk immunoreactivity. Of the number of hypothalamic hcrt-1 immunoreactive neurons identified ipsilateral to the NTS injection site (1207 ± 78), 32.3 ± 2.3% co-expressed L-Enk immunoreactivity and of these, 2.6 ± 1.1% were retrogradely labeled with FG. Hcrt-1/L-Enk neurons projecting to NTS were found mainly within the perifornical region. In the second series, the region of caudal NTS found to contain axons that co-expressed hcrt-1 and L-Enk immunoreactivity was microinjected with a combination of hcrt-1 and DADL in α-chloralose anesthetized Wistar rats. Microinjection of DADL into NTS elicited depressor and bradycardia responses similar to those elicited by microinjection of hcrt-1. An hcrt-1 injection immediately after the DADL injection elicited an almost twofold increase in the magnitude of the depressor and bradycardia responses compared to those elicited by hcrt-1 alone. Prior injections of the non-specific opioid receptor antagonist naloxone or the specific opioid δ-receptor antagonist ICI 154,129 significantly attenuated the cardiovascular responses to the combined hcrt-1-DADL injections. Taken together, these data suggest that activation of hypothalamic-opioidergic neuronal systems contribute to the NTS hcrt-1 induced cardiovascular responses, and that this descending hypothalamo

  17. A Relationship between Reduced Nucleus Accumbens Shell and Enhanced Lateral Hypothalamic Orexin Neuronal Activation in Long-Term Fructose Bingeing Behavior

    Science.gov (United States)

    Rorabaugh, Jacki M.; Stratford, Jennifer M.; Zahniser, Nancy R.

    2014-01-01

    Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc) shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM) display signatures of hedonic feeding including bingeing and altered DA receptor (R) numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day) exposure to the IAM, rats given 8–12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR). This activation was negatively correlated with orexin (Orx) neuron activation in the lateral hypothalamus/perifornical area (LH/PeF), a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day) access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p.) equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  18. A relationship between reduced nucleus accumbens shell and enhanced lateral hypothalamic orexin neuronal activation in long-term fructose bingeing behavior.

    Directory of Open Access Journals (Sweden)

    Jacki M Rorabaugh

    Full Text Available Fructose accounts for 10% of daily calories in the American diet. Fructose, but not glucose, given intracerebroventricularly stimulates homeostatic feeding mechanisms within the hypothalamus; however, little is known about how fructose affects hedonic feeding centers. Repeated ingestion of sucrose, a disaccharide of fructose and glucose, increases neuronal activity in hedonic centers, the nucleus accumbens (NAc shell and core, but not the hypothalamus. Rats given glucose in the intermittent access model (IAM display signatures of hedonic feeding including bingeing and altered DA receptor (R numbers within the NAc. Here we examined whether substituting fructose for glucose in this IAM produces bingeing behavior, alters DA Rs and activates hedonic and homeostatic feeding centers. Following long-term (21-day exposure to the IAM, rats given 8-12% fructose solutions displayed fructose bingeing but unaltered DA D1R or D2R number. Fructose bingeing rats, as compared to chow bingeing controls, exhibited reduced NAc shell neuron activation, as determined by c-Fos-immunoreactivity (Fos-IR. This activation was negatively correlated with orexin (Orx neuron activation in the lateral hypothalamus/perifornical area (LH/PeF, a brain region linking homeostatic to hedonic feeding centers. Following short-term (2-day access to the IAM, rats exhibited bingeing but unchanged Fos-IR, suggesting only long-term fructose bingeing increases Orx release. In long-term fructose bingeing rats, pretreatment with the Ox1R antagonist SB-334867 (30 mg/kg; i.p. equally reduced fructose bingeing and chow intake, resulting in a 50% reduction in calories. Similarly, in control rats, SB-334867 reduced chow/caloric intake by 60%. Thus, in the IAM, Ox1Rs appear to regulate feeding based on caloric content rather than palatability. Overall, our results, in combination with the literature, suggest individual monosaccharides activate distinct neuronal circuits to promote feeding behavior

  19. Topography of subnuclei of the hypothalamic paraventricular nucleus in rats and sensitivity of their neurons to insulin defficiency

    International Nuclear Information System (INIS)

    Goufman, E.I.

    1985-01-01

    This investigation was undertaken to study the reaction of paraventricular nuclei (PVN) subnuclei to insulin deficiency and to elevation of the blood glucose level under conditions of experimental alloxan diabetes. Experiments were carried out on 15 control and 15 experimental mature male Wistar rats. The state of the carbohydrate metabolism of the diabetic and control animals was judged by the blood glucose and radioimmune insulin levels. The results of these investigations show that both magnocellular and parvocellular neurons of PVN react to alloxan diabetes, which supports the hypothesis that PVN of the hypothalamus participates in the control of carbohydrate metabolism

  20. Nucleus Ruber of Actinopterygians.

    Science.gov (United States)

    Nakayama, Tomoya; Miyajima, Satoshi; Nishino, Hirotaka; Narita, Junya; Abe, Hideki; Yamamoto, Naoyuki

    2016-01-01

    Nucleus ruber is known as an important supraspinal center that controls forelimb movements in tetrapods, and the rubral homologue may serve similar functions in fishes (motor control of pectoral fin). However, two apparently different structures have been identified as 'nucleus ruber' in actinopterygians. One is nucleus ruber of Goldstein (1905) (NRg), and the other nucleus ruber of Nieuwenhuys and Pouwels (1983) (NRnp). It remains unclear whether one of these nuclei (or perhaps both) is homologous to tetrapod nucleus ruber. To resolve this issue from a phylogenetic point of view, we have investigated the distribution of tegmental neurons retrogradely labeled from the spinal cord in eight actinopterygian species. We also investigated the presence/absence of the two nuclei with Nissl- or Bodian-stained brain section series of an additional 28 actinopterygian species by comparing the morphological features of candidate rubral neurons with those of neurons revealed by the tracer studies. Based on these analyses, the NRg was identified in all actinopterygians investigated in the present study, while the NRnp appears to be absent in basal actinopterygians. The phylogenetic distribution pattern indicates that the NRg is the more likely homologue of nucleus ruber, and the NRnp may be a derived nucleus that emerged during the course of actinopterygian evolution. © 2016 S. Karger AG, Basel.

  1. IGF-1 deficiency causes atrophic changes associated with upregulation of VGluT1 and downregulation of MEF2 transcription factors in the mouse cochlear nuclei.

    Science.gov (United States)

    Fuentes-Santamaría, V; Alvarado, J C; Rodríguez-de la Rosa, L; Murillo-Cuesta, S; Contreras, J; Juiz, J M; Varela-Nieto, I

    2016-03-01

    Insulin-like growth factor 1 (IGF-1) is a neurotrophic protein that plays a crucial role in modulating neuronal function and synaptic plasticity in the adult brain. Mice lacking the Igf1 gene exhibit profound deafness and multiple anomalies in the inner ear and spiral ganglion. An issue that remains unknown is whether, in addition to these peripheral abnormalities, IGF-1 deficiency also results in structural changes along the central auditory pathway that may contribute to an imbalance between excitation and inhibition, which might be reflected in abnormal auditory brainstem responses (ABR). To assess such a possibility, we evaluated the morphological and physiological alterations in the cochlear nucleus complex of the adult mouse. The expression and distribution of the vesicular glutamate transporter 1 (VGluT1) and the vesicular inhibitory transporter (VGAT), which were used as specific markers for labeling excitatory and inhibitory terminals, and the involvement of the activity-dependent myocyte enhancer factor 2 (MEF2) transcription factors in regulating excitatory synapses were assessed in a 4-month-old mouse model of IGF-1 deficiency and neurosensorial deafness (Igf1 (-/-) homozygous null mice). The results demonstrate decreases in the cochlear nucleus area and cell size along with cell loss in the cochlear nuclei of the deficient mouse. Additionally, our results demonstrate that there is upregulation of VGluT1, but not VGAT, immunostaining and downregulation of MEF2 transcription factors together with increased wave II amplitude in the ABR recording. Our observations provide evidence of an abnormal neuronal cytoarchitecture in the cochlear nuclei of Igf1 (-/-) null mice and suggest that the increased efficacy of glutamatergic synapses might be mediated by MEF2 transcription factors.

  2. Multichannel cochlear implantation in the scala vestibuli.

    Science.gov (United States)

    Lin, Karen; Marrinan, Michelle S; Waltzman, Susan B; Roland, J Thomas

    2006-08-01

    Sensorineural hearing loss resulting from otosclerosis, meningitis, chronic otitis media, autoimmune ear disease, and trauma can be associated with partial or total obstruction of the cochlear scalae. Multichannel cochlear implantation may be difficult in a cochlea with an obstructed scala tympani. The purpose of this study is to determine the safety and efficacy of scala tympani electrode insertion. Retrospective chart review. Academic medical center. Eight children and adults with profound sensorineural hearing loss who underwent cochlear implantation with known scala vestibuli electrode array insertion were subjects for this study. Eight study subjects underwent implantation: five with the Nucleus 24RCS (Contour) device and three with the Nucleus 24M device. Imaging findings, operative findings, and age-appropriate speech perception testing. All patients had full electrode insertion. Various obstructive patterns on computed tomography and magnetic resonance imaging were found, and there was a range of speech perception results. All but one patient improved based on age-appropriate monosyllabic word and sentence tests. Scala vestibuli multielectrode insertion is a viable alternative when scala tympani insertion is not possible because of abnormal anatomy or anatomical changes secondary to disease or previous implantation. We will also present an algorithm of options for decision making for implantation when encountering cochlear obstruction and difficult electrode insertion.

  3. The cochlear implant as a tinnitus treatment.

    Science.gov (United States)

    Vallés-Varela, Héctor; Royo-López, Juan; Carmen-Sampériz, Luis; Sebastián-Cortés, José M; Alfonso-Collado, Ignacio

    2013-01-01

    Tinnitus is a symptom of high prevalence in patients with cochlear pathology. We studied the evolution of tinnitus in patients undergoing unilateral cochlear implantation for treatment of profound hearing loss. This was a longitudinal, retrospective study of patients that underwent unilateral cochlear implantation and who had bilateral tinnitus. Tinnitus was assessed quantitatively and qualitatively before surgery and at 6 and 12 months after surgery. We evaluated 20 patients that underwent unilateral cochlear implantation with a Nucleus(®) CI24RE Contour Advance™ electrode device. During the periods in which the device was in operation, improvement or disappearance of tinnitus was evidenced in the ipsilateral ear in 65% of patients, and in the contralateral ear, in 50%. In periods in which the device was disconnected, improvement or disappearance of tinnitus was found in the ipsilateral ear in 50% of patients, and in the ear contralateral to the implant in 45% of the patients. In 10% of the patients, a new tinnitus appeared in the ipsilateral ear. The patients with profound hearing loss and bilateral tinnitus treated with unilateral cochlear implantation improved in a high percentage of cases, in the ipsilateral ear and in the contralateral ear. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  4. Coherence of neuronal firing of the entopeduncular nucleus with motor cortex oscillatory activity in the 6-OHDA rat model of Parkinson's disease with levodopa-induced dyskinesias.

    Science.gov (United States)

    Jin, Xingxing; Schwabe, Kerstin; Krauss, Joachim K; Alam, Mesbah

    2016-04-01

    The pathophysiological mechanisms leading to dyskinesias in Parkinson's disease (PD) after long-term treatment with levodopa remain unclear. This study investigates the neuronal firing characteristics of the entopeduncular nucleus (EPN), the rat equivalent of the human globus pallidus internus and output nucleus of the basal ganglia, and its coherence with the motor cortex (MCx) field potentials in the unilateral 6-OHDA rat model of PD with and without levodopa-induced dyskinesias (LID). 6-hydroxydopamine-lesioned hemiparkinsonian (HP) rats, 6-OHDA-lesioned HP rats with LID (HP-LID) rats, and naïve controls were used for recording of single-unit activity under urethane (1.4 g/kg, i.p) anesthesia in the EPN "on" and "off" levodopa. Over the MCx, the electrocorticogram output was recorded. Analysis of single-unit activity in the EPN showed enhanced firing rates, burst activity, and irregularity compared to naïve controls, which did not differ between drug-naïve HP and HP-LID rats. Analysis of EPN spike coherence and phase-locked ratio with MCx field potentials showed a shift of low (12-19 Hz) and high (19-30 Hz) beta oscillatory activity between HP and HP-LID groups. EPN theta phase-locked ratio was only enhanced in HP-LID compared to HP rats. Overall, levodopa injection had no stronger effect in HP-LID rats than in HP rats. Altered coherence and changes in the phase lock ratio of spike and local field potentials in the beta range may play a role for the development of LID.

  5. The basic circuit of the IC: tectothalamic neurons with different patterns of synaptic organization send different messages to the thalamus

    Science.gov (United States)

    Ito, Tetsufumi; Oliver, Douglas L.

    2012-01-01

    The inferior colliculus (IC) in the midbrain of the auditory system uses a unique basic circuit to organize the inputs from virtually all of the lower auditory brainstem and transmit this information to the medial geniculate body (MGB) in the thalamus. Here, we review the basic circuit of the IC, the neuronal types, the organization of their inputs and outputs. We specifically discuss the large GABAergic (LG) neurons and how they differ from the small GABAergic (SG) and the more numerous glutamatergic neurons. The somata and dendrites of LG neurons are identified by axosomatic glutamatergic synapses that are lacking in the other cell types and exclusively contain the glutamate transporter VGLUT2. Although LG neurons are most numerous in the central nucleus of the IC (ICC), an analysis of their distribution suggests that they are not specifically associated with one set of ascending inputs. The inputs to ICC may be organized into functional zones with different subsets of brainstem inputs, but each zone may contain the same three neuron types. However, the sources of VGLUT2 axosomatic terminals on the LG neuron are not known. Neurons in the dorsal cochlear nucleus, superior olivary complex, intermediate nucleus of the lateral lemniscus, and IC itself that express the gene for VGLUT2 only are the likely origin of the dense VGLUT2 axosomatic terminals on LG tectothalamic neurons. The IC is unique since LG neurons are GABAergic tectothalamic neurons in addition to the numerous glutamatergic tectothalamic neurons. SG neurons evidently target other auditory structures. The basic circuit of the IC and the LG neurons in particular, has implications for the transmission of information about sound through the midbrain to the MGB. PMID:22855671

  6. Long-term subregion-specific encoding of enhanced ethanol intake by D1DR medium spiny neurons of the nucleus accumbens.

    Science.gov (United States)

    Renteria, Rafael; Buske, Tavanna R; Morrisett, Richard A

    2018-03-01

    The nucleus accumbens (NAc) is a critical component of the mesocorticolimbic system and is involved in mediating the motivational and reinforcing aspects of ethanol consumption. Chronic intermittent ethanol (CIE) exposure is a reliable model to induce ethanol dependence and increase volitional ethanol consumption in mice. Following a CIE-induced escalation of ethanol consumption, NMDAR (N-methyl-D-aspartate receptor)-dependent long-term depression in D1 dopamine receptor expressing medium spiny neurons of the NAc shell was markedly altered with no changes in plasticity in D1 dopamine receptor medium spiny neurons from the NAc core. This disruption of plasticity persisted for up to 2 weeks after cessation of ethanol access. To determine if changes in AMPA receptor (AMPAR) composition contribute to this ethanol-induced neuroadaptation, we monitored the rectification of AMPAR excitatory postsynaptic currents (EPSCs). We observed a marked decrease in the rectification index in the NAc shell, suggesting the presence of GluA2-lacking AMPARs. There was no change in the amplitude of spontaneous EPSCs (sEPSCs), but there was a transient increase in sEPSC frequency in the NAc shell. Using the paired pulse ratio, we detected a similar transient increase in the probability of neurotransmitter release. With no change in sEPSC amplitude, the change in the rectification index suggests that GluA2-containing AMPARs are removed and replaced with GluA2-lacking AMPARs in the NAc shell. This CIE-induced alteration in AMPAR subunit composition may contribute to the loss of NMDAR-dependent long-term depression in the NAc shell and therefore may constitute a critical neuroadaptive response underlying the escalation of ethanol intake in the CIE model. © 2017 Society for the Study of Addiction.

  7. Lesion of the commissural nucleus of the solitary tract/A2 noradrenergic neurons facilitates the activation of angiotensinergic mechanisms in response to hemorrhage.

    Science.gov (United States)

    Freiria-Oliveira, A H; Blanch, G T; De Paula, P M; Menani, J V; Colombari, D S A

    2013-12-19

    In the present study, we investigated the effects of lesions of A2 neurons of the commissural nucleus of the solitary tract (cNTS) alone or combined with the blockade of angiotensinergic mechanisms on the recovery of arterial pressure (AP) to hemorrhage in conscious rats. Male Holtzman rats (280-320g) received an injection of anti-dopamine-beta-hydroxylase-saporin (12.6ng/60nl; cNTS/A2-lesion, n=28) or immunoglobulin G (IgG)-saporin (12.6ng/60nl, sham, n=24) into the cNTS and 15-21days later had a stainless steel cannula implanted in the lateral ventricle. After 6days, rats were submitted to hemorrhage (four blood withdrawals, 2ml/300g of body weight every 10min). Both cNTS/A2-lesioned and sham rats had similar hypotension to hemorrhage (-62±7 and -73±7mmHg, respectively), however cNTS/A2-lesioned rats rapidly recovered from hypotension (-5±3mmHg at 30min), whereas sham rats did not completely recover until the end of the recording (-20±3mmHg at 60min). Losartan (angiotensin type 1 receptor antagonist) injected intracerebroventricularly (100μg/1μl) or intravenously (i.v.) (10mg/kg of body weight) impaired the recovery of AP in cNTS/A2-lesioned rats (-24±6 and -35±7mmHg at 30min, respectively). In sham rats, only i.v. losartan affected the recovery of AP (-39±6mmHg at 60min). The results suggest that lesion of the A2 neurons in the cNTS facilitates the activation of the angiotensinergic pressor mechanisms in response to hemorrhage. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Postsynaptic potentials recorded in neurons of the cat's lateral geniculate nucleus following electrical stimulation of the optic chiasm.

    Science.gov (United States)

    Bloomfield, S A; Sherman, S M

    1988-12-01

    1. We recorded intracellularly from X and Y cells of the cat's lateral geniculate nucleus and measured the postsynaptic potentials (PSPs) evoked from electrical stimulation of the optic chiasm. We used an in vivo preparation and computer averaged the PSPs to enhance their signal-to-noise ratio. 2. The vast majority (46 of 50) of our sample of X and Y cells responded to stimulation of the optic chiasm with an excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP); these were tentatively identified as relay cells. We quantified several parameters of these PSPs, including amplitude, latency, time to peak (i.e., rise time), and duration. 3. Among the relay cells, the latencies of both the EPSP and action potential evoked by optic chiasm stimulation were shorter in Y cells than in X cells. Furthermore, the difference between the latencies of the EPSP and action potential was shorter for Y cells than for X cells. This means that the EPSPs generated in Y cells reached threshold for generation of action potentials faster than did those in X cells. The EPSPs of Y cells also displayed larger amplitudes and faster rise times than did those in X cells, but neither of these distinctions was sufficient to explain the shorter latency difference between the EPSP and action potential for Y cells. 4. The EPSPs recorded in relay Y cells had longer durations than did those in relay X cells. Our data suggest that the subsequent IPSP actively terminates the EPSP, which, in turn, suggests that the time interval between EPSP and IPSP onsets is longer in Y cells than in X cells. Furthermore, we found that, for individual Y cells, the latency and duration of the evoked EPSP were inversely related. These observations lead to the conclusion that the latency of IPSPs activated from the optic chiasm is relatively constant among Y cells and thus independent of the EPSP latencies. Thus the excitation and inhibition produced in individual geniculate Y

  9. How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

    Science.gov (United States)

    Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

    2018-01-01

    Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

  10. Ethanol up-regulates nucleus accumbens neuronal activity dependent pentraxin (Narp): implications for alcohol-induced behavioral plasticity.

    Science.gov (United States)

    Ary, Alexis W; Cozzoli, Debra K; Finn, Deborah A; Crabbe, John C; Dehoff, Marlin H; Worley, Paul F; Szumlinski, Karen K

    2012-06-01

    Neuronal activity dependent pentraxin (Narp) interacts with α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) glutamate receptors to facilitate excitatory synapse formation by aggregating them at established synapses. Alcohol is well-characterized to influence central glutamatergic transmission, including AMPA receptor function. Herein, we examined the influence of injected and ingested alcohol upon Narp protein expression, as well as basal Narp expression in mouse lines selectively bred for high blood alcohol concentrations under limited access conditions. Alcohol up-regulated accumbens Narp levels, concomitant with increases in levels of the GluR1 AMPA receptor subunit. However, accumbens Narp or GluR1 levels did not vary as a function of selectively bred genotype. We next employed a Narp knock-out (KO) strategy to begin to understand the behavioral relevance of alcohol-induced changes in protein expression in several assays of alcohol reward. Compared to wild-type mice, Narp KO animals: fail to escalate daily intake of high alcohol concentrations under free-access conditions; shift their preference away from high alcohol concentrations with repeated alcohol experience; exhibit a conditioned place-aversion in response to the repeated pairing of 3 g/kg alcohol with a distinct environment and fail to exhibit alcohol-induced locomotor hyperactivity following repeated alcohol treatment. Narp deletion did not influence the daily intake of either food or water, nor did it alter any aspect of spontaneous or alcohol-induced motor activity, including the development of tolerance to its motor-impairing effects with repeated treatment. Taken together, these data indicate that Narp induction, and presumably subsequent aggregation of AMPA receptors, may be important for neuroplasticity within limbic subcircuits mediating or maintaining the rewarding properties of alcohol. Published by Elsevier Inc.

  11. Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity

    NARCIS (Netherlands)

    Garcia-Falgueras, Alicia; Ligtenberg, Lisette; Kruijver, Frank P. M.; Swaab, Dick F.

    2011-01-01

    The intermediate nucleus (InM) in the preoptic area of the human brain, also known as the sexually dimorphic nucleus of the preoptic area (SDN-POA) and the interstitial nucleus of the anterior hypothalamus-1 (INAH-1) is explored here. We investigated its population of galanin-immunoreactive (Gal-Ir)

  12. Nucleus--nucleus potential

    International Nuclear Information System (INIS)

    Jaqaman, H.R.

    1977-01-01

    The nucleus--nucleus interaction is studied within the framework of the generator coordinate method that permits an easy incorporation of the full effects of antisymmetrization. It is found that the interaction, as far as the elastic scattering problem is concerned, can be described by a simple effective potential that is equivalent to the original many-body (and hence non-local) problem. The potential is obtained by dividing the wavefunction into a long-range part and a short-range part and requiring the former to satisfy a Schroedinger equation. This enables avoiding dealing with the troublesome short-range part of the wavefunction and provides a direct link with the optical model so that the potential obtained here is equivalent to the real part of the optical potential (the imaginary part is not investigated). The effective potential is found to consist of three parts: an interaction term between the nucleons belonging to different nuclei, a kinetic energy term due to the change in the intrinsic kinetic energy of the system as a result of the antisymmetrization, and finally an l-dependent part. The kinetic energy term is found to be very repulsive and effectively gives a hard core, and is calculated for the α--α and 16 O-- 16 O cases. The full potential is calculated for the α--α case for the S, D, and G partial waves and then used to calculate the corresponding phase shifts that are then compared with experimental results and other microscopic calculations. Finally, some recent results and analyses of fusion and deep inelastic reactions are reviewed that seem to indicate the presence of a hard core in the nucleus--nucleus potential. Such a hard core is present in the potential obtained in the sudden approximation

  13. Protein kinase A-dependent Neuronal Nitric Oxide Synthase Activation Mediates the Enhancement of Baroreflex Response by Adrenomedullin in the Nucleus Tractus Solitarii of Rats

    Directory of Open Access Journals (Sweden)

    Ho I-Chun

    2011-05-01

    Full Text Available Abstract Background Adrenomedullin (ADM exerts its biological functions through the receptor-mediated enzymatic mechanisms that involve protein kinase A (PKA, or neuronal nitric oxide synthase (nNOS. We previously demonstrated that the receptor-mediated cAMP/PKA pathway involves in ADM-enhanced baroreceptor reflex (BRR response. It remains unclear whether ADM may enhance BRR response via activation of nNOS-dependent mechanism in the nucleus tractus solitarii (NTS. Methods Intravenous injection of phenylephrine was administered to evoke the BRR before and at 10, 30, and 60 min after microinjection of the test agents into NTS of Sprague-Dawley rats. Western blotting analysis was used to measure the level and phosphorylation of proteins that involved in BRR-enhancing effects of ADM (0.2 pmol in NTS. The colocalization of PKA and nNOS was examined by immunohistochemical staining and observed with a laser confocal microscope. Results We found that ADM-induced enhancement of BRR response was blunted by microinjection of NPLA or Rp-8-Br-cGMP, a selective inhibitor of nNOS or protein kinase G (PKG respectively, into NTS. Western blot analysis further revealed that ADM induced an increase in the protein level of PKG-I which could be attenuated by co-microinjection with the ADM receptor antagonist ADM22-52 or NPLA. Moreover, we observed an increase in phosphorylation at Ser1416 of nNOS at 10, 30, and 60 min after intra-NTS administration of ADM. As such, nNOS/PKG signaling may also account for the enhancing effect of ADM on BRR response. Interestingly, biochemical evidence further showed that ADM-induced increase of nNOS phosphorylation was prevented by co-microinjection with Rp-8-Br-cAMP, a PKA inhibitor. The possibility of PKA-dependent nNOS activation was substantiated by immunohistochemical demonstration of co-localization of PKA and nNOS in putative NTS neurons. Conclusions The novel finding of this study is that the signal transduction cascade that

  14. Role of PKA signaling in D2 receptor-expressing neurons in the core of the nucleus accumbens in aversive learning.

    Science.gov (United States)

    Yamaguchi, Takashi; Goto, Akihiro; Nakahara, Ichiro; Yawata, Satoshi; Hikida, Takatoshi; Matsuda, Michiyuki; Funabiki, Kazuo; Nakanishi, Shigetada

    2015-09-08

    The nucleus accumbens (NAc) serves as a key neural substrate for aversive learning and consists of two distinct subpopulations of medium-sized spiny neurons (MSNs). The MSNs of the direct pathway (dMSNs) and the indirect pathway (iMSNs) predominantly express dopamine (DA) D1 and D2 receptors, respectively, and are positively and negatively modulated by DA transmitters via Gs- and Gi-coupled cAMP-dependent protein kinase A (PKA) signaling cascades, respectively. In this investigation, we addressed how intracellular PKA signaling is involved in aversive learning in a cell type-specific manner. When the transmission of either dMSNs or iMSNs was unilaterally blocked by pathway-specific expression of transmission-blocking tetanus toxin, infusion of PKA inhibitors into the intact side of the NAc core abolished passive avoidance learning toward an electric shock in the indirect pathway-blocked mice, but not in the direct pathway-blocked mice. We then examined temporal changes in PKA activity in dMSNs and iMSNs in behaving mice by monitoring Förster resonance energy transfer responses of the PKA biosensor with the aid of microendoscopy. PKA activity was increased in iMSNs and decreased in dMSNs in both aversive memory formation and retrieval. Importantly, the increased PKA activity in iMSNs disappeared when aversive memory was prevented by keeping mice in the conditioning apparatus. Furthermore, the increase in PKA activity in iMSNs by aversive stimuli reflected facilitation of aversive memory retention. These results indicate that PKA signaling in iMSNs plays a critical role in both aversive memory formation and retention.

  15. Activation of mGluR5 induces spike afterdepolarization and enhanced excitability in medium spiny neurons of the nucleus accumbens by modulating persistent Na+ currents

    Science.gov (United States)

    D’Ascenzo, Marcello; Podda, Maria Vittoria; Fellin, Tommaso; Azzena, Gian Battista; Haydon, Philip; Grassi, Claudio

    2009-01-01

    The involvement of metabotropic glutamate receptors type 5 (mGluR5) in drug-induced behaviours is well-established but limited information is available on their functional roles in addiction-relevant brain areas like the nucleus accumbens (NAc). This study demonstrates that pharmacological and synaptic activation of mGluR5 increases the spike discharge of medium spiny neurons (MSNs) in the NAc. This effect was associated with the appearance of a slow afterdepolarization (ADP) which, in voltage-clamp experiments, was recorded as a slowly inactivating inward current. Pharmacological studies showed that ADP was elicited by mGluR5 stimulation via G-protein-dependent activation of phospholipase C and elevation of intracellular Ca2+ levels. Both ADP and spike aftercurrents were significantly inhibited by the Na+ channel-blocker, tetrodotoxin (TTX). Moreover, the selective blockade of persistent Na+ currents (INaP), achieved by NAc slice pre-incubation with 20 nm TTX or 10 μm riluzole, significantly reduced the ADP amplitude, indicating that this type of Na+ current is responsible for the mGluR5-dependent ADP. mGluR5 activation also produced significant increases in INaP, and the pharmacological blockade of this current prevented the mGluR5-induced enhancement of spike discharge. Collectively, these data suggest that mGluR5 activation upregulates INaP in MSNs of the NAc, thereby inducing an ADP that results in enhanced MSN excitability. Activation of mGluR5 will significantly alter spike firing in MSNs in vivo, and this effect could be an important mechanism by which these receptors mediate certain aspects of drug-induced behaviours. PMID:19433572

  16. Long-lasting alterations in membrane properties, K+ currents and glutamatergic synaptic currents of nucleus accumbens medium spiny neurons in a rat model of alcohol dependence

    Directory of Open Access Journals (Sweden)

    Igor eSpigelman

    2012-06-01

    Full Text Available Chronic alcohol exposure causes marked changes in reinforcement mechanisms and motivational state that are thought to contribute to the development of cravings and relapse during protracted withdrawal. The nucleus accumbens (NAcc is a key structure of the mesolimbic dopaminergic reward system. Although the NAcc plays an important role in mediating alcohol-seeking behaviors, little is known about the molecular mechanisms underlying alcohol-induced neuroadaptive changes in NAcc function. The aim of this study was to investigate the effects of chronic intermittent ethanol (CIE treatment, a rat model of alcohol withdrawal and dependence, on intrinsic electrical membrane properties and glutamatergic synaptic transmission of medium spiny neurons (MSNs in the NAcc core during protracted withdrawal. We show that CIE treatment followed by prolonged withdrawal increased the inward rectification of MSNs observed at hyperpolarized potentials. In addition, MSNs from CIE-treated animals displayed a lower input resistance, faster action potentials (APs and larger fast afterhyperpolarizations (fAHPs than MSNs from vehicle-treated animals, all suggestive of increases in K+-channel conductances. Significant increases in the Cs+-sensitive inwardly-rectifying K+-current accounted for the increased input resistance, while increases in the A-type K+-current accounted for the faster APs and increased fAHPs in MSNs from CIE rats. We also show that the amplitude and the conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR-mediated mEPSCs were enhanced in CIE-treated animals due to an increase in a small fraction of functional postsynaptic GluA2-lacking AMPARs. These long-lasting modifications of excitability and excitatory synaptic receptor function of MSNs in the NAcc core could play a critical role in the neuroadaptive changes underlying alcohol withdrawal and dependence.

  17. Glycogen synthase kinase 3 beta alters anxiety-, depression-, and addiction-related behaviors and neuronal activity in the nucleus accumbens shell

    Science.gov (United States)

    Crofton, Elizabeth J.; Nenov, Miroslav N.; Zhang, Yafang; Scala, Federico; Page, Sean A.; McCue, David L.; Li, Dingge; Hommel, Jonathan D.; Laezza, Fernanda; Green, Thomas A.

    2017-01-01

    Psychiatric disorders such as anxiety, depression and addiction are often comorbid brain pathologies thought to share common mechanistic biology. As part of the cortico-limbic circuit, the nucleus accumbens shell (NAcSh) plays a fundamental role in integrating information in the circuit, such that modulation of NAcSh circuitry alters anxiety, depression, and addiction-related behaviors. Intracellular kinase cascades in the NAcSh have proven important mediators of behavior. To investigate glycogen-synthase kinase 3 (GSK3) beta signaling in the NAcSh in vivo we knocked down GSK3beta expression with a novel adeno-associated viral vector (AAV2) and assessed changes in anxiety- and depression-like behavior and cocaine self-administration in GSK3beta knockdown rats. GSK3beta knockdown reduced anxiety-like behavior while increasing depression-like behavior and cocaine self-administration. Correlative electrophysiological recordings in acute brain slices were used to assess the effect of AAV-shGSK3beta on spontaneous firing and intrinsic excitability of tonically active interneurons (TANs), cells required for input and output signal integration in the NAcSh and for processing reward-related behaviors. Loose-patch recordings showed that TANs transduced by AAV-shGSK3beta exhibited reduction in tonic firing and increased spike half width. When assessed by whole-cell patch clamp recordings these changes were mirrored by reduction in action potential firing and accompanied by decreased hyperpolarization-induced depolarizing sag potentials, increased action potential current threshold, and decreased maximum rise time. These results suggest that silencing of GSK3beta in the NAcSh increases depression- and addiction-related behavior, possibly by decreasing intrinsic excitability of TANs. However, this study does not rule out contributions from other neuronal sub-types. PMID:28126496

  18. Trends in cochlear implants.

    Science.gov (United States)

    Zeng, Fan-Gang

    2004-01-01

    More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic aspects of cochlear implants, focusing on their psychophysical, speech, music, and cognitive performance. This report also forecasts clinical and research trends related to presurgical evaluation, fitting protocols, signal processing, and postsurgical rehabilitation in cochlear implants. Finally, a future landscape in amplification is presented that requires a unique, yet complementary, contribution from hearing aids, middle ear implants, and cochlear implants to achieve a total solution to the entire spectrum of hearing loss treatment and management.

  19. [Cochlear implant in patients with congenital malformation of the inner ear].

    Science.gov (United States)

    Wan, Liang-cai; Guo, Meng-he; Qian, Yu-hong; Liu, Shuang-xiu; Zhang, Hong-zheng; Chen, Shuai-jun; Chen, Hao; Gong, Jian

    2009-10-01

    To summarize the clinical experience with multi-channel cochlear implantation in patients with inner ear malformations and evaluate and the outcomes of speech rehabilitation. A retrospective study was conducted in 295 patients receiving cochlear implantation from 1998 to 2007, including 25 patients with large vestibular aqueduct syndrome (LVAS), 9 with Modini malformation, and 5 with common cavity deformity. All the patients received the Nucleus24 cochlear implants. In LVAS cases, 4 had Nucleus 24R (ST) implants, 8 had Contuor implants, 10 had Contuor Advance, and the remaining cases used Nucleus24(M) straight-electrode implants. Severe gusher appeared in 3 cases of LVAS, and perilymph fluctuation were seen in other 15 cases. Four patients with Mondini malformation and 2 with common cavity malformation also experienced severe gusher, but the electrodes were inserted smoothly in all the patients without postoperative facial paralysis or cerebrospinal fluid leakage. The hearing threshold in these patients was similar to that in patients with normal cochlear structure. After speech rehabilitation for over 6 months, the abilities of speech discrimination and spoken language improved in all the cases in comparison with the preoperative lingual functions. Multi-channel cochlear implantation can be performed in patients with inner ear malformation, but should not be attempted in patients with poor cochlear and cochlear nerve development. A comprehensive pre-operative radiographic and audiological evaluation is essential.

  20. Benefits and Risks of Cochlear Implants

    Science.gov (United States)

    ... and Medical Procedures Implants and Prosthetics Cochlear Implants Benefits and Risks of Cochlear Implants Share Tweet Linkedin ... the Use of Cochlear Implants What are the Benefits of Cochlear Implants? For people with implants: Hearing ...

  1. Cochlear injury and adaptive plasticity of the auditory cortex

    Directory of Open Access Journals (Sweden)

    ANNA R. eFETONI

    2015-02-01

    Full Text Available Growing evidence suggests that cochlear stressors as noise exposure and aging can induce homeostatic/maladaptive changes in the central auditory system from the brainstem to the cortex. Studies centered on such changes have revealed several mechanisms that operate in the context of sensory disruption after insult (noise trauma, drug- or age-related injury. The oxidative stress is central to current theories of induced sensory neural hearing loss and aging, and interventions to attenuate the hearing loss are based on antioxidant agent. The present review addresses the recent literature on the alterations in hair cells and spiral ganglion neurons due to noise-induced oxidative stress in the cochlea, as well on the impact of cochlear damage on the auditory cortex neurons. The emerging image emphasizes that noise-induced deafferentation and upward spread of cochlear damage is associated with the altered dendritic architecture of auditory pyramidal neurons. The cortical modifications may be reversed by treatment with antioxidants counteracting the cochlear redox imbalance. These findings open new therapeutic approaches to treat the functional consequences of the cortical reorganization following cochlear damage.

  2. Selective alterations of NMDAR function and plasticity in D1 and D2 medium spiny neurons in the nucleus accumbens shell following chronic intermittent ethanol exposure.

    Science.gov (United States)

    Renteria, Rafael; Maier, Esther Y; Buske, Tavanna R; Morrisett, Richard A

    2017-01-01

    A major mouse model widely adopted in recent years to induce pronounced ethanol intake is the ethanol vapor model known as "CIE" or "Chronic Intermittent Ethanol." One critical question concerning this model is whether the rapid induction of high blood ethanol levels for such short time periods is sufficient to induce alterations in N-methyl-d-aspartate receptor (NMDAR) function which may contribute to excessive ethanol intake. In this study, we determined whether such short term intermittent ethanol exposure modulates NMDAR function as well as other prominent electrophysiological properties and the expression of plasticity in both D1 (D1+) and D2 (D1-) dopamine receptor expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc) shell. To distinguish between the two subtypes of MSNs in the NAc we treated Drd1a-TdTomato transgenic mice with CIE vapor and electrophysiological recordings were conducted 24 h after the last vapor exposure. To investigate CIE induced alterations in plasticity, long-term depression (LTD) was induced by pairing low frequency stimulation (LFS) with post synaptic depolarization. In ethanol naïve mice, LFS induced synaptic depression (LTD) was apparent exclusively in D1+ MSNs. Whereas in slices prepared from CIE treated mice, LFS induced synaptic potentiation (LTP) in D1+ MSNs. Furthermore, following CIE exposure, LFS now produced LTD in D1- MSNs. We found that CIE exposure induced an increase in excitability in D1+ MSNs with no change in D1- MSNs. After CIE, we found a significant increase in spontaneous EPSCs (sEPSCs) frequency in D1+ but not D1- MSNs suggesting alterations in baseline α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) mediated signaling. CIE induced changes in NMDAR function were measured using the NMDA/AMPA ratio and input-output curves of isolated NMDAR currents. We observed a significant increase in NMDAR function in D1+ MSNs and a decrease in D1- MSNs after ethanol vapor exposure. The

  3. Effects of chronic furosemide on central neural hyperactivity and cochlear thresholds after cochlear trauma in guinea pig

    Directory of Open Access Journals (Sweden)

    Wilhelmina eMulders

    2014-08-01

    Full Text Available Increased neuronal spontaneous firing rates have been observed throughout the central auditory system after trauma to the cochlea and this hyperactivity is believed to be associated with the phantom perception of tinnitus. Previously we have shown in an animal model of hearing loss, that an acute injection with furosemide can significantly decrease hyperactivity after cochlear trauma and eliminate behavioural evidence of tinnitus of early onset. However, furosemide also has the potential to affect cochlear thresholds. In this paper we measured the effects of a chronic (daily injections for 7 days furosemide treatment on the spontaneous firing rate of inferior colliculus neurons and on cochlear thresholds in order to establish whether a beneficial effect on hyperactivity can be obtained without causing additional hearing loss. Guinea pigs were exposed to a 10 kHz, 124dB, 2 hour acoustic trauma, and after 5 days of recovery, were given daily i.p. injections of 80mg/kg furosemide or an equivalent amount of saline. The activity of single IC neurons was recorded 24 hours following the last injection. The furosemide treatment had no effect on cochlear thresholds compared to saline injections but did result in significant reductions in spontaneous firing rates recorded in inferior colliculus. These results that suggest a long term beneficial effect of furosemide on hyperactivity after cochlear trauma may be achievable without detrimental effects on hearing, which is important when considering therapeutic potential.

  4. Trends in Cochlear Implants

    OpenAIRE

    Zeng, Fan-Gang

    2004-01-01

    More than 60,000 people worldwide use cochlear implants as a means to restore functional hearing. Although individual performance variability is still high, an average implant user can talk on the phone in a quiet environment. Cochlear-implant research has also matured as a field, as evidenced by the exponential growth in both the patient population and scientific publication. The present report examines current issues related to audiologic, clinical, engineering, anatomic, and physiologic as...

  5. High-Frequency Stimulation of the Subthalamic Nucleus Activates Motor Cortex Pyramidal Tract Neurons by a Process Involving Local Glutamate, GABA and Dopamine Receptors in Hemi-Parkinsonian Rats.

    Science.gov (United States)

    Chuang, Chi-Fen; Wu, Chen-Wei; Weng, Ying; Hu, Pei-San; Yeh, Shin-Rung; Chang, Yen-Chung

    2018-04-30

    Deep brain stimulation (DBS) is widely used to treat advanced Parkinson’s disease (PD). Here, we investigated how DBS applied on the subthalamic nucleus (STN) influenced the neural activity in the motor cortex. Rats, which had the midbrain dopaminergic neurons partially depleted unilaterally, called the hemi-Parkinsonian rats, were used as a study model. c-Fos expression in the neurons was used as an indicator of neural activity. Application of high-frequency stimulation (HFS) upon the STN was used to mimic the DBS treatment. The motor cortices in the two hemispheres of hemi-Parkinsonian rats were found to contain unequal densities of c-Fos-positive (Fos+) cells, and STN-HFS rectified this bilateral imbalance. In addition, STN-HFS led to the intense c-Fos expression in a group of motor cortical neurons which exhibited biochemical and anatomical characteristics resembling those of the pyramidal tract (PT) neurons sending efferent projections to the STN. The number of PT neurons expressing high levels of c-Fos was significantly reduced by local application of the antagonists of non-N-methyl-D-aspartate (non-NMDA) glutamate receptors, gammaaminobutyric acid A (GABAA) receptors and dopamine receptors in the upper layers of the motor cortex. The results indicate that the coincident activations of synapses and dopamine receptors in the motor cortex during STN-HFS trigger the intense expression of c-Fos of the PT neurons. The implications of the results on the cellular mechanism underlying the therapeutic effects of STN-DBS on the movement disorders of PD are also discussed.

  6. Co-localization of high-affinity neurotrophin receptors in nucleus basalis of Meynert neurons and their differential reduction in Alzheimer's disease

    NARCIS (Netherlands)

    Salehi, A.; Verhaagen, J.; Dijkhuizen, P. A.; Swaab, D. F.

    1996-01-01

    It has been suggested that degeneration of neurons in Alzheimer's disease is the result of diminished trophic support. However, so far no evidence has been forwarded that neuronal degeneration in Alzheimer's disease is causally related to insufficient production of neurotrophins. The present study

  7. Long-Term Recordings of Arcuate Nucleus Kisspeptin Neurons Reveal Patterned Activity That Is Modulated by Gonadal Steroids in Male Mice.

    Science.gov (United States)

    Vanacker, Charlotte; Moya, Manuel Ricu; DeFazio, R Anthony; Johnson, Michael L; Moenter, Suzanne M

    2017-10-01

    Pulsatile release of gonadotropin-releasing hormone (GnRH) is key to fertility. Pulse frequency is modulated by gonadal steroids and likely arises subsequent to coordination of GnRH neuron firing activity. The source of rhythm generation and the site of steroid feedback remain critical unanswered questions. Arcuate neurons that synthesize kisspeptin, neurokinin B, and dynorphin (KNDy) may be involved in both of these processes. We tested the hypotheses that action potential firing in KNDy neurons is episodic and that gonadal steroids regulate this pattern. Targeted extracellular recordings were made of green fluorescent protein-identified KNDy neurons in brain slices from adult male mice that were intact, castrated, or castrated and treated with estradiol or dihydrotestosterone (DHT). KNDy neurons exhibited marked peaks and nadirs in action potential firing activity during recordings lasting 1 to 3.5 hours. Peaks, identified by Cluster analysis, occurred more frequently in castrated than intact mice, and either estradiol or DHT in vivo or blocking neurokinin type 3 receptor in vitro restored peak frequency to intact levels. The frequency of peaks in firing rate and estradiol regulation of this frequency is similar to that observed for GnRH neurons, whereas DHT suppressed firing in KNDy but not GnRH neurons. We further examined the patterning of action potentials to identify bursts that may be associated with increased neuromodulator release. Burst frequency and duration are increased in castrated compared with intact and steroid-treated mice. The observation that KNDy neurons fire in an episodic manner that is regulated by steroid feedback is consistent with a role for these neurons in GnRH pulse generation and regulation. Copyright © 2017 Endocrine Society.

  8. Projections from the raphe nuclei to the suprachiasmatic nucleus of the rat

    DEFF Research Database (Denmark)

    Hay-Schmidt, Anders; Vrang, N.; Larsen, P.J.

    2003-01-01

    Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)......Hypothalamus, Circadian rhythm, Serotonin, Nucleus, Neuronal connections, Phaseolus vulgaris-leucoagglutinin (PHA-L), Cholera toxin (ChB)...

  9. Projections from the cochlear nuclei in the mustache bat, Pteronotus parnellii

    International Nuclear Information System (INIS)

    Zook, J.M.; Casseday, J.H.

    1985-01-01

    Ascending projections of the cochlear nuclei in the mustache bat were analyzed by anterograde transport of [ 3 H]-leucine and by retrograde transport of HRP. The authors were particularly interested in pathways to two parts of the system: (1) to the medial superior olive, because this nucleus is missing in most echolocating bats, but appears to be present in the mustache bat, and (2) to the intermediate and ventral nuclei of the lateral lemniscus, because these nuclei are hypertrophied and highly differentiated in all echolocating bats that we have examined. The results show a highly systematic projection from the anteroventral cochlear nucleus to all of the auditory nuclei in the brain stem. After an injection of [ 3 H]-leucine in the anterior and dorsal part of the anteroventral cochlear nucleus, presumably in a region sensitive to low frequencies, label is seen in the following locations: ipsilateral to the injection in the lateral part of the lateral superior olive; bilaterally in the dorsal part of the medial superior olive; contralateral to the injection in the dorsal parts of the intermediate and ventral nuclei of the lateral lemniscus; and in the anterolateral part of the central nucleus of the inferior colliculus. After an injection of [ 3 H]-leucine in a posterior part of the anteroventral cochlear nucleus, presumably in a region sensitive to high frequencies, labeling is in the same set of nuclei, but within each nucleus the label is now in a different location. Projections from the entire anteroventral cochlear nucleus to the inferior colliculus are confined to the ventral two-thirds of the central nucleus

  10. Cerebellar projections to the red nucleus and inferior olive originate from separate populations of neurons in the rat: A non-fluorescent double labeling study

    NARCIS (Netherlands)

    T.M. Teune (Thea); J. van der Burg (Johannes); T.J.H. Ruigrok (Tom)

    1995-01-01

    textabstractIn the rat, the extent of collateralization of projections from the cerebellar nuclei to the red nucleus and inferior olive was investigated using a retrograde double labeling technique. The combination of tracers selected, cholera toxin-β-subunit and WGA-BSA-gold, not only enabled the

  11. A circuit for detection of interaural time differences in the nucleus laminaris of turtles.

    Science.gov (United States)

    Willis, Katie L; Carr, Catherine E

    2017-11-15

    The physiological hearing range of turtles is approximately 50-1000 Hz, as determined by cochlear microphonics ( Wever and Vernon, 1956a). These low frequencies can constrain sound localization, particularly in red-eared slider turtles, which are freshwater turtles with small heads and isolated middle ears. To determine if these turtles were sensitive to interaural time differences (ITDs), we investigated the connections and physiology of their auditory brainstem nuclei. Tract tracing experiments showed that cranial nerve VIII bifurcated to terminate in the first-order nucleus magnocellularis (NM) and nucleus angularis (NA), and the NM projected bilaterally to the nucleus laminaris (NL). As the NL received inputs from each side, we developed an isolated head preparation to examine responses to binaural auditory stimulation. Magnocellularis and laminaris units responded to frequencies from 100 to 600 Hz, and phase-locked reliably to the auditory stimulus. Responses from the NL were binaural, and sensitive to ITD. Measures of characteristic delay revealed best ITDs around ±200 μs, and NL neurons typically had characteristic phases close to 0, consistent with binaural excitation. Thus, turtles encode ITDs within their physiological range, and their auditory brainstem nuclei have similar connections and cell types to other reptiles. © 2017. Published by The Company of Biologists Ltd.

  12. [Cochlear implant in patients with congenital malformation of inner ear].

    Science.gov (United States)

    Han, Dong-yi; Wu, Wen-ming; Xi, Xin; Huang, De-liang; Yang, Wei-yan

    2004-02-01

    To study surgical difficulty and key of the cochlear implant in patients with congenital malformation of inner ear. The cochlear implantations were performed in our department from Jan. 2001 to Apr. 2003 for 18 patients with the malformation of inner ear. In this series, there were 11 cases of large vestibular aqueduct syndrome (LVAS), 3 cases of Waardenberg syndrome, 3 cases of Mondini malformation, and 1 case of Usher syndrome. All 18 patients accepted the Nucleus 24-channel cochlear implantations, including Nucleus straight electrode in 13 cases but Contour implantation in 5 cases of LVAS. During operations, leakage of perilymph but not cerebrospinal fluid (CSF) from the open of scala tympani occurred in 11 cases of LVAS, however, the electrode was inserted successfully. The abnormalities of round window occurred in one of 3 cases of Waardenberg syndrome and 3 cases of Mondini malformation, respectively. The cochlear implant could be conducted successfully for the LVAS, and the postoperative effect was same as the ones for the deafness persons with normal development of inner ear. However, for the patients with Mondini syndrome and common cavity, it is important to accurately assess the extent of abnormalities in the inner ear and accompanied malformation before operation, and to evaluate the full extent of difficulties of the operation in order to minimize the risk of CSF leakage and meningitis.

  13. Activity in a premotor cortical nucleus of zebra finches is locally organized and exhibits auditory selectivity in neurons but not in glia.

    Directory of Open Access Journals (Sweden)

    Michael H Graber

    Full Text Available Motor functions are often guided by sensory experience, most convincingly illustrated by complex learned behaviors. Key to sensory guidance in motor areas may be the structural and functional organization of sensory inputs and their evoked responses. We study sensory responses in large populations of neurons and neuron-assistive cells in the songbird motor area HVC, an auditory-vocal brain area involved in sensory learning and in adult song production. HVC spike responses to auditory stimulation display remarkable preference for the bird's own song (BOS compared to other stimuli. Using two-photon calcium imaging in anesthetized zebra finches we measure the spatio-temporal structure of baseline activity and of auditory evoked responses in identified populations of HVC cells. We find strong correlations between calcium signal fluctuations in nearby cells of a given type, both in identified neurons and in astroglia. In identified HVC neurons only, auditory stimulation decorrelates ongoing calcium signals, less for BOS than for other sound stimuli. Overall, calcium transients show strong preference for BOS in identified HVC neurons but not in astroglia, showing diversity in local functional organization among identified neuron and astroglia populations.

  14. Transcanal labyrinthectomy for intractable vertigo after unilateral cochlear implantation.

    Science.gov (United States)

    Heidenreich, Katherine D; Basura, Gregory J; Zwolan, Teresa A; El-Kashlan, Hussam K; Telian, Steven A

    2011-10-01

    Document the use of transcanal labyrinthectomy to treat disabling attacks of vertigo after unilateral cochlear implantation. A 46-year-old woman with severe-profound bilateral sensorineural hearing loss secondary to enlarged vestibular aqueducts underwent cochlear implantation for her right ear with a Nucleus Freedom device. The surgery was uneventful, and postoperative imaging confirmed that the electrode was positioned properly. She developed episodic vertigo 10 to 14 days after the implant surgery, which failed to improve with aggressive vestibular rehabilitation therapy. Plugging of the round window for possible perilymphatic fistula did not relieve her symptoms. Right transcanal labyrinthectomy supplemented by filling the vestibule with gentamicin-soaked Gelfoam and then a customized vestibular rehabilitation program. Comparison of vestibular symptoms and cochlear implant performance before and after transcanal labyrinthectomy. The patient had immediate relief of symptoms, and the function of the cochlear implant was not adversely affected. Transcanal labyrinthectomy may be an effective method to ablate the vestibular end organ after unilateral cochlear implantation. It can offer relief of disabling vertigo without adversely affecting the performance of the implant.

  15. Characterization of Cochlear, Vestibular and Cochlear-Vestibular Electrically Evoked Compound Action Potentials in Patients with a Vestibulo-Cochlear Implant

    Directory of Open Access Journals (Sweden)

    T. A. K. Nguyen

    2017-11-01

    Full Text Available The peripheral vestibular system is critical for the execution of activities of daily life as it provides movement and orientation information to motor and sensory systems. Patients with bilateral vestibular hypofunction experience a significant decrease in quality of life and have currently no viable treatment option. Vestibular implants could eventually restore vestibular function. Most vestibular implant prototypes to date are modified cochlear implants to fast-track development. These use various objective measurements, such as the electrically evoked compound action potential (eCAP, to supplement behavioral information. We investigated whether eCAPs could be recorded in patients with a vestibulo-cochlear implant. Specifically, eCAPs were successfully recorded for cochlear and vestibular setups, as well as for mixed cochlear-vestibular setups. Similarities and slight differences were found for the recordings of the three setups. These findings demonstrated the feasibility of eCAP recording with a vestibulo-cochlear implant. They could be used in the short term to reduce current spread and avoid activation of non-targeted neurons. More research is warranted to better understand the neural origin of vestibular eCAPs and to utilize them for clinical applications.

  16. Effect of dietary salt intake on epithelial Na+ channels (ENaC) in vasopressin magnocellular neurosecretory neurons in the rat supraoptic nucleus.

    Science.gov (United States)

    Sharma, Kaustubh; Haque, Masudul; Guidry, Richard; Ueta, Yoichi; Teruyama, Ryoichi

    2017-09-01

    A growing body of evidence suggests that epithelial Na + channels (ENaCs) in the brain play a significant role in the regulation of blood pressure; however, the brain structures that mediate the effect are not well understood. Because vasopressin (VP) neurons play a pivotal role in coordinating neuroendocrine and autonomic responses to maintain cardiovascular homeostasis, a basic understanding of the regulation and activity of ENaC in VP neurons is of great interest. We show that high dietary salt intake caused an increase in the expression and activity of ENaC which resulted in the steady state depolarization of VP neurons. The results help us understand one of the mechanisms underlying how dietary salt intake affects the activity of VP neurons via ENaC activity. All three epithelial Na + channel (ENaC) subunits (α, β and γ) are located in vasopressin (VP) magnocellular neurons in the hypothalamic supraoptic (SON) and paraventricular nuclei. Our previous study demonstrated that ENaC mediates a Na + leak current that affects the steady state membrane potential in VP neurons. In the present study, we evaluated the effect of dietary salt intake on ENaC regulation and activity in VP neurons. High dietary salt intake for 7 days caused an increase in expression of β- and γENaC subunits in the SON and the translocation of αENaC immunoreactivity towards the plasma membrane. Patch clamp experiments on hypothalamic slices showed that the mean amplitude of the putative ENaC currents was significantly greater in VP neurons from animals that were fed a high salt diet compared with controls. The enhanced ENaC current contributed to the more depolarized basal membrane potential observed in VP neurons in the high salt diet group. These findings indicate that high dietary NaCl intake enhances the expression and activity of ENaCs, which augments synaptic drive by depolarizing the basal membrane potential close to the action potential threshold during hormonal demand. However

  17. Cochlear pathology in chronic suppurative otitis media.

    Science.gov (United States)

    Walby, A P; Barrera, A; Schuknecht, H F

    1983-01-01

    Chronic suppurative otitis media (COM) is reported to cause elevation of bone-conduction thresholds either by damage to cochlear sensorineural structures or by alteration in the mechanics of sound transmission in the ear. A retrospective study was made of the medical records of 87 patients with unilateral uncomplicated COM to document that abnormality in bone conduction does exist. In a separate study the cochlear pathology in 12 pairs of temporal bones with unilateral COM was studied by light microscopy. Infected ears showed higher than normal mean bone-conduction thresholds by amounts ranging from 1 dB at 500 Hz to 9.5 dB at 4,000 Hz. The temporal bones showed no greater loss of specialized sensorineural structures in infected ears than in normal control ears. Because there is no evidence that COM caused destruction of hair cells or cochlear neurons, alteration in the mechanics of sound transmission becomes a more plausible explanation for the hearing losses.

  18. The Expression of Fos, Jun and AP-1 DNA Binding Activity in Rat Supraoptic Nucleus Neurons Following Acute Versus Repeated Osmotic Stimulation

    Science.gov (United States)

    1995-06-22

    energy . Dr. Griemley - for agreeing to sit on my committee and providing the advice. vii least, for his Thank you for Drs. Steven Bassnett, Rita Dhawan...encouragement. your time, energy and patience. viii TABLE OF CONTENTS Page Approval Sheet i Copyright Statement ii Abstract ’ iii Title Page...D.A., and Murphy,D. 1990. Regulation of c-fos and c- jun expression in the rat supraoptic nucleus. Cell. Mol. Neurobio . 10: 435-445 Castel, M., Gainer

  19. Inter- and intracellular relationship of substance P-containing neurons with serotonin and GABA in the dorsal raphe nucleus: combination of autoradiographic and immunocytochemical techniques

    International Nuclear Information System (INIS)

    Magoul, R.; Onteniente, B.; Oblin, A.; Calas, A.

    1986-01-01

    Double-labeling experiments were performed at the electron microscopic level in the dorsal raphe nucleus of rat, in order to study the inter- and intracellular relationship of substance P with gamma-aminobutyric acid (GABA) and serotonin. Autoradiography for either [ 3 H]serotonin or [ 3 H]GABA was coupled, on the same tissue section, with peroxidase-antiperoxidase immunocytochemistry for substance P in colchicine-treated animals. Intercellular relationships were represented by synaptic contacts made by [ 3 H]serotonin-labeled terminals on substance P-containing somata and dendrites, and by substance P-containing terminals on [ 3 H]GABA-labeled cells. Intracellular relationships were suggested by the occurrence of the peptide within [ 3 H]serotonin-containing and [ 3 H]GABA-containing cell bodies and fibers. Doubly labeled varicosities of the two kinds were also observed in the supraependymal plexus adjacent to the dorsal raphe nucleus. The results demonstrated that, in addition to reciprocal synaptic interactions made by substance P with serotonin and GABA, the dorsal raphe nucleus is the site of intracellular relationships between the peptide and either the amine or the amino acid

  20. Long latency auditory evoked potentials in children with cochlear implants: systematic review.

    Science.gov (United States)

    Silva, Liliane Aparecida Fagundes; Couto, Maria Inês Vieira; Matas, Carla Gentile; Carvalho, Ana Claudia Martinho de

    2013-11-25

    The aim of this study was to analyze the findings on Cortical Auditory Evoked Potentials in children with cochlear implant through a systematic literature review. After formulation of research question and search of studies in four data bases with the following descriptors: electrophysiology (eletrofisiologia), cochlear implantation (implante coclear), child (criança), neuronal plasticity (plasticidade neuronal) and audiology (audiologia), were selected articles (original and complete) published between 2002 and 2013 in Brazilian Portuguese or English. A total of 208 studies were found; however, only 13 contemplated the established criteria and were further analyzed; was made data extraction for analysis of methodology and content of the studies. The results described suggest rapid changes in P1 component of Cortical Auditory Evoked Potentials in children with cochlear implants. Although there are few studies on the theme, cochlear implant has been shown to produce effective changes in central auditory path ways especially in children implanted before 3 years and 6 months of age.

  1. Distribution of glutamatergic, GABAergic, and glycinergic neurons in the auditory pathways of macaque monkeys.

    Science.gov (United States)

    Ito, T; Inoue, K; Takada, M

    2015-12-03

    Macaque monkeys use complex communication calls and are regarded as a model for studying the coding and decoding of complex sound in the auditory system. However, little is known about the distribution of excitatory and inhibitory neurons in the auditory system of macaque monkeys. In this study, we examined the overall distribution of cell bodies that expressed mRNAs for VGLUT1, and VGLUT2 (markers for glutamatergic neurons), GAD67 (a marker for GABAergic neurons), and GLYT2 (a marker for glycinergic neurons) in the auditory system of the Japanese macaque. In addition, we performed immunohistochemistry for VGLUT1, VGLUT2, and GAD67 in order to compare the distribution of proteins and mRNAs. We found that most of the excitatory neurons in the auditory brainstem expressed VGLUT2. In contrast, the expression of VGLUT1 mRNA was restricted to the auditory cortex (AC), periolivary nuclei, and cochlear nuclei (CN). The co-expression of GAD67 and GLYT2 mRNAs was common in the ventral nucleus of the lateral lemniscus (VNLL), CN, and superior olivary complex except for the medial nucleus of the trapezoid body, which expressed GLYT2 alone. In contrast, the dorsal nucleus of the lateral lemniscus, inferior colliculus, thalamus, and AC expressed GAD67 alone. The absence of co-expression of VGLUT1 and VGLUT2 in the medial geniculate, medial superior olive, and VNLL suggests that synaptic responses in the target neurons of these nuclei may be different between rodents and macaque monkeys. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Neurokinin-1 receptor blocker CP-99 994 improved emesis induced by cisplatin via regulating the activity of gastric distention responsive neurons in the dorsal motor nucleus of vagus and enhancing gastric motility in rats.

    Science.gov (United States)

    Sun, X; Xu, L; Guo, F; Luo, W; Gao, S; Luan, X

    2017-10-01

    Nowadays, chemotherapy induced nausea and vomiting (CINV) is still common in patients with cancer. It was reported that substance P mediated CINV via neurokinin-1 (NK 1 ) receptor and antagonists of NK 1 receptor has been proved useful for treating CINV but the mechanism are not fully understood. This study aimed to examine the role of NK 1 receptor blocker, CP-99 994, when administrated into dorsal motor nucleus of vagus (DMNV), on the cisplatin-induced emesis in rats and the possible mechanism. Rats' kaolin intake, food intake, and bodyweight were recorded every day; gastric contraction activity was recorded in conscious rats through a force transducer implanted into the stomach; gastric emptying was monitored using the phenol red method; single unit extracellular firing in the DMNV were recorded. DMNV microinjection of CP-99 994 reduced the changes of increased kaolin consumption and suppressed food intake in cisplatin-treated rats; enhanced the gastric contraction activity dose-dependently in control and cisplatin-treated rats but enhanced gastric emptying only in cisplatin-treated rats; reduced the firing rate of gastric distention inhibited (GD-I) neurons but increased the firing rate of GD excited (GD-E) neurons in the DMNV. The effects of CP-99 994 on gastric motility and neuronal activity were stronger in cisplatin-treated rats than those of control rats. Our results suggested that CP-99 994 could improve emesis induced by cisplatin by regulating gastric motility and gastric related neuronal activity in the DMNV. © 2017 John Wiley & Sons Ltd.

  3. STD-dependent and independent encoding of input irregularity as spike rate in a computational model of a cerebellar nucleus neuron

    NARCIS (Netherlands)

    J. Luthman (Johannes); F.E. Hoebeek (Freek); R. Maex (Reinoud); N. Davey (Neil); R. Adams (Rod); C.I. de Zeeuw (Chris); V. Steuber (Volker)

    2011-01-01

    textabstractNeurons in the cerebellar nuclei (CN) receive inhibitory inputs from Purkinje cells in the cerebellar cortex and provide the major output from the cerebellum, but their computational function is not well understood. It has recently been shown that the spike activity of Purkinje cells is

  4. The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

    DEFF Research Database (Denmark)

    Ruffault, Pierre Louis; D’Autréaux, Fabien; Hayes, John A.

    2015-01-01

    . Photostimulation of these neurons entrains the respiratory rhythm. Conversely, abrogating expression of Atoh1 or Phox2b or glutamatergic transmission in these cells curtails the phrenic nerve response to low pH in embryonic preparations and abolishes the respiratory chemoreflex in behaving animals. Thus, the RTN...

  5. In vitro and in vivo responses of saccular and caudal nucleus neurons in the grassfrog (Rana temporaria)

    DEFF Research Database (Denmark)

    Christensen-Dalsgaard, J; Walkowiak, W

    1999-01-01

    We present results from in vitro and in vivo studies of response properties of neurons in the saccular and caudal nuclei in the frog. In the in vitro studies the saccular nerve of the isolated brain was stimulated with electrical pulses. In the in vivo experiments, the neurons were stimulated...... by dorso-ventral vibrations of the intact animal. We identified six response types: (1) primary-like cells with short latencies and follow repetition rates up to 100 Hz; (2) phasic cells responding only to the first pulse in a train; (3) bursting cells firing several spikes in response to any stimulation......; (4) late responders with very long latencies; (5) integrator cells showing facilitated responses, and (6) inhibitory cells inhibited by saccular nerve stimulation.The cells have comparable sensitivity and frequency characteristics to the primary fibres (BF 10-80 Hz, thresholds from 0.01 cm/s2...

  6. Challenges in Improving Cochlear Implant Performance and Accessibility.

    Science.gov (United States)

    Zeng, Fan-Gang

    2017-08-01

    Here I identify two gaps in cochlear implants that have been limiting their performance and acceptance. First, cochlear implant performance has remained largely unchanged, despite the number of publications tripling per decade in the last 30 years. Little has been done so far to address a fundamental limitation in the electrode-to-neuron interface, with the electrode size being a thousand times larger than the neuron diameter while the number of electrodes being a thousand times less. Both the small number and the large size of electrodes produce broad spatial activation and poor frequency resolution that limit current cochlear implant performance. Second, a similarly rapid growth in cochlear implant volume has not produced an expected decrease in unit price in the same period. The high cost contributes to low market penetration rate, which is about 20% in developed countries and less than 1% in developing countries. I will discuss changes needed in both research strategy and business practice to close the gap between prosthetic and normal hearing as well as that between haves and have-nots.

  7. Cochlear implantation in Mondini dysplasia.

    Science.gov (United States)

    Daneshi, Ahmad; Hassanzadeh, Saeid; Abasalipour, Parvaneh; Emamdjomeh, Hessamaddin; Farhadi, Mohammad

    2003-01-01

    The use of cochlear implantation to treat patients with inner ear malformations such as Mondini dysplasia has been increasingly successful. Until now, conventional hearing aids in these patients have not performed well. Consequently, the hearing problem for patients with this condition has been somewhat improved with the use of cochlear implants. Various results of cochlear implantation have been reported in these patients so far. This is a report of 5 patients with Mondini malformation who have undergone cochlear implant surgery. Copyright 2003 S. Karger AG, Basel

  8. Restoration of quinine-stimulated Fos-immunoreactive neurons in the central nucleus of the amygdala and gustatory cortex following reinnervation or cross-reinnervation of the lingual taste nerves in rats.

    Science.gov (United States)

    King, Camille Tessitore; Garcea, Mircea; Spector, Alan C

    2014-08-01

    Remarkably, when lingual gustatory nerves are surgically rerouted to inappropriate taste fields in the tongue, some taste functions recover. We previously demonstrated that quinine-stimulated oromotor rejection reflexes and neural activity (assessed by Fos immunoreactivity) in subregions of hindbrain gustatory nuclei were restored if the posterior tongue, which contains receptor cells that respond strongly to bitter compounds, was cross-reinnervated by the chorda tympani nerve. Such functional recovery was not seen if instead, the anterior tongue, where receptor cells are less responsive to bitter compounds, was cross-reinnervated by the glossopharyngeal nerve, even though this nerve typically responds robustly to bitter substances. Thus, recovery depended more on the taste field being reinnervated than on the nerve itself. Here, the distribution of quinine-stimulated Fos-immunoreactive neurons in two taste-associated forebrain areas was examined in these same rats. In the central nucleus of the amygdala (CeA), a rostrocaudal gradient characterized the normal quinine-stimulated Fos response, with the greatest number of labeled cells situated rostrally. Quinine-stimulated neurons were found throughout the gustatory cortex, but a "hot spot" was observed in its anterior-posterior center in subregions approximating the dysgranular/agranular layers. Fos neurons here and in the rostral CeA were highly correlated with quinine-elicited gapes. Denervation of the posterior tongue eliminated, and its reinnervation by either nerve restored, numbers of quinine-stimulated labeled cells in the rostralmost CeA and in the subregion approximating the dysgranular gustatory cortex. These results underscore the remarkable plasticity of the gustatory system and also help clarify the functional anatomy of neural circuits activated by bitter taste stimulation. © 2014 Wiley Periodicals, Inc.

  9. Electrophysiological evidence for the presence of NR2C subunits of N-methyl-D-aspartate receptors in rat neurons of the nucleus tractus solitarius

    Directory of Open Access Journals (Sweden)

    V. Baptista

    2005-01-01

    Full Text Available The nucleus tractus solitarius (NTS plays an important role in the control of autonomic reflex functions. Glutamate, acting on N-methyl-D-aspartate (NMDA and non-NMDA ionotropic receptors, is the major neurotransmitter in this nucleus, and the relative contribution of each receptor to signal transmission is unclear. We have examined NMDA excitatory postsynaptic currents (NMDA-EPSCs in the subpostremal NTS using the whole cell patch clamp technique on a transverse brainstem slice preparation. The NMDA-EPSCs were evoked by stimulation of the solitary tract over a range of membrane potentials. The NMDA-EPSCs, isolated pharmacologically, presented the characteristic outward rectification and were completely blocked by 50 µM DL-2-amino-5-phosphonopentanoic acid. The I-V relationship of the NMDA response shows that current, with a mean (± SEM amplitude of -41.2 ± 5.5 pA, is present even at a holding potential of -60 mV, suggesting that the NMDA receptors are weakly blocked by extracellular Mg2+ at near resting membrane potentials. This weak block can also be inferred from the value of 0.67 ± 0.17 for parameter delta obtained from a fit of the Woodhull equation to the I-V relationship. The maximal inward current measured on the I-V relationship was at -38.7 ± 4.2 mV. The decay phase of the NMDA currents was fitted with one exponential function with a decay time constant of 239 ± 51 and 418 ± 80 ms at a holding potential of -60 and +50 mV, respectively, which became slower with depolarization (e-fold per 145 mV. The biophysical properties of the NMDA receptors observed in the present study suggest that these receptors in the NTS contain NR2C subunits and may contribute to the synaptic signal integration.

  10. Efter cochlear implant

    DEFF Research Database (Denmark)

    Højen, Anders

    Dit barn har netop fået et cochlear implant. Hvad nu? Skal barnet fokusere udelukkende på at lære talt sprog, eller skal det også lære/fortsætte med tegnsprog eller støttetegn? Det er et vanskeligt spørgsmål, og før valget foretages, er det vigtigt at vurdere hvilke konsekvenser valget har, dels...... for den sproglige udvikling isoleret set, og dels for barnets udvikling ud fra en helhedsbetragtning. Dette indlæg fokuserer på, hvilke forventninger man kan have til cochlear implant-brugeres sproglige udvikling med talt sprog alene, hhv. med to sprog (tale og tegn). Disse forventninger er baseret på...

  11. Modelling Cochlear Mechanics

    Directory of Open Access Journals (Sweden)

    Guangjian Ni

    2014-01-01

    Full Text Available The cochlea plays a crucial role in mammal hearing. The basic function of the cochlea is to map sounds of different frequencies onto corresponding characteristic positions on the basilar membrane (BM. Sounds enter the fluid-filled cochlea and cause deflection of the BM due to pressure differences between the cochlear fluid chambers. These deflections travel along the cochlea, increasing in amplitude, until a frequency-dependent characteristic position and then decay away rapidly. The hair cells can detect these deflections and encode them as neural signals. Modelling the mechanics of the cochlea is of help in interpreting experimental observations and also can provide predictions of the results of experiments that cannot currently be performed due to technical limitations. This paper focuses on reviewing the numerical modelling of the mechanical and electrical processes in the cochlea, which include fluid coupling, micromechanics, the cochlear amplifier, nonlinearity, and electrical coupling.

  12. Cochlear implantation in patients with bilateral cochlear trauma.

    Science.gov (United States)

    Serin, Gediz Murat; Derinsu, Ufuk; Sari, Murat; Gergin, Ozgül; Ciprut, Ayça; Akdaş, Ferda; Batman, Cağlar

    2010-01-01

    Temporal bone fracture, which involves the otic capsule, can lead to complete loss of auditory and vestibular functions, whereas the patients without fractures may experience profound sensorineural hearing loss due to cochlear concussion. Cochlear implant is indicated in profound sensorineural hearing loss due to cochlear trauma but who still have an intact auditory nerve. This is a retrospective review study. We report 5 cases of postlingually deafened patients caused by cochlear trauma, who underwent cochlear implantation. Preoperative and postoperative hearing performance will be presented. These patients are cochlear implanted after the cochlear trauma in our department between 2001 and 2006. All patients performed very well with their implants, obtained open-set speech understanding. They all became good telephone users after implantation. Their performance in speech understanding was comparable to standard postlingual adult patients implanted. Cochlear implantation is an effective aural rehabilitation in profound sensorineural hearing loss caused by temporal bone trauma. Preoperative temporal bone computed tomography, magnetic resonance imaging, and promontorium stimulation testing are necessary to make decision for the surgery and to determine the side to be implanted. Surgery could be challenging and complicated because of anatomical irregularity. Moreover, fibrosis and partial or total ossification within the cochlea must be expected. Copyright 2010. Published by Elsevier Inc.

  13. A software tool for analyzing multichannel cochlear implant signals.

    Science.gov (United States)

    Lai, Wai Kong; Bögli, Hans; Dillier, Norbert

    2003-10-01

    A useful and convenient means to analyze the radio frequency (RF) signals being sent by a speech processor to a cochlear implant would be to actually capture and display them with appropriate software. This is particularly useful for development or diagnostic purposes. sCILab (Swiss Cochlear Implant Laboratory) is such a PC-based software tool intended for the Nucleus family of Multichannel Cochlear Implants. Its graphical user interface provides a convenient and intuitive means for visualizing and analyzing the signals encoding speech information. Both numerical and graphic displays are available for detailed examination of the captured CI signals, as well as an acoustic simulation of these CI signals. sCILab has been used in the design and verification of new speech coding strategies, and has also been applied as an analytical tool in studies of how different parameter settings of existing speech coding strategies affect speech perception. As a diagnostic tool, it is also useful for troubleshooting problems with the external equipment of the cochlear implant systems.

  14. Suprachiasmatic Nucleus Interaction with the Arcuate Nucleus; Essential for Organizing Physiological Rhythms

    NARCIS (Netherlands)

    Buijs, Frederik N.; Guzmán-Ruiz, Mara; León-Mercado, Luis; Basualdo, Mari Carmen; Escobar, Carolina; Kalsbeek, Andries; Buijs, Ruud M.

    2017-01-01

    The suprachiasmatic nucleus (SCN) is generally considered the master clock, independently driving all circadian rhythms. We recently demonstrated the SCN receives metabolic and cardiovascular feedback adeptly altering its neuronal activity. In the present study, we show that microcuts effectively

  15. The suprachiasmatic nucleus-paraventricular nucleus interactions: a bridge to the neuroendocrine and autonomic nervous system

    NARCIS (Netherlands)

    Buijs, R. M.; Hermes, M. H.; Kalsbeek, A.

    1998-01-01

    Vasopressin (VP) is one of the principal neurotransmitters of the suprachiasmatic nucleus (SCN). By means of anatomical, physiological and electrophysiological techniques we have demonstrated that VP containing pathways from the SCN serve to affect neuroendocrine and 'autonomic' neurons in the

  16. The nucleus

    International Nuclear Information System (INIS)

    Marano, S.

    1998-01-01

    In 1911 E.Rutherford discovered the nucleus. Since then the nucleus has been investigated with more and more powerful tools but it remains the main field of study of nuclear physics. As it is impossible to take into account the interaction of all the nucleons, a theory based on the hypothesis that each nucleon undergoes an average interaction force has been set up. 2 representations have emerged: the Skyrme force and the Gogny force. Both representations match experimental results but are unable to describe fission yields or the multi-fragmentation of very hot nuclei. The mean-field theory can predict the shape of the nuclei according to its energy level. An experimental program involving the Vivitron accelerator and the Euroball detector is due to begin to validate it. By bombarding targets with exotic nuclei nuclear physicists detect new structures and test their collision models. About ten years ago nuclear halos were observed with lithium 11 nuclei. In this nucleus 2 neutrons move in a space larger than the nucleus itself. This discovery has triggered the elaboration of new theories based on nuclear clusters. At very high temperatures the mean-field theory predicts that nuclear matter acts as a fluid. Following the nuclei temperature different ways of decay appear: first evaporation then multi-fragmentation and vaporization. This ultimate stage occurs around 100 milliard celsius degree temperature when the nuclei decays in a multitude of light particles. Isomeric states are studied and could be seen as a way of storing energy. In a very pedagogical way this article gives information to understand the challenges that face nuclear physics today and highlights the contributions of Cea in this field. (A.C.)

  17. Structural dynamics of the cell nucleus

    Science.gov (United States)

    Wiegert, Simon; Bading, Hilmar

    2011-01-01

    Neuronal morphology plays an essential role in signal processing in the brain. Individual neurons can undergo use-dependent changes in their shape and connectivity, which affects how intracellular processes are regulated and how signals are transferred from one cell to another in a neuronal network. Calcium is one of the most important intracellular second messengers regulating cellular morphologies and functions. In neurons, intracellular calcium levels are controlled by ion channels in the plasma membrane such as NMDA receptors (NMDARs), voltage-gated calcium channels (VGCCs) and certain α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) as well as by calcium exchange pathways between the cytosol and internal calcium stores including the endoplasmic reticulum and mitochondria. Synaptic activity and the subsequent opening of ligand and/or voltage-gated calcium channels can initiate cytosolic calcium transients which propagate towards the cell soma and enter the nucleus via its nuclear pore complexes (NPCs) embedded in the nuclear envelope. We recently described the discovery that in hippocampal neurons the morphology of the nucleus affects the calcium dynamics within the nucleus. Here we propose that nuclear infoldings determine whether a nucleus functions as an integrator or detector of oscillating calcium signals. We outline possible ties between nuclear mophology and transcriptional activity and discuss the importance of extending the approach to whole cell calcium signal modeling in order to understand synapse-to-nucleus communication in healthy and dysfunctional neurons. PMID:21738832

  18. Selective retrograde labeling of lateral olivocochlear neurons in the brainstem based on preferential uptake of 3H-D-aspartic acid in the cochlea

    International Nuclear Information System (INIS)

    Ryan, A.F.; Schwartz, I.R.; Helfert, R.H.; Keithley, E.; Wang, Z.X.

    1987-01-01

    We have previously shown that perfusion of the gerbil cochlea with probe concentrations of 3 H-D-aspartic acid (D-ASP) results in immediate, selective labeling of 50-60% of the efferent terminals under the inner hair cells, presumably by high-affinity uptake. The present study was undertaken to determine the origin of these endings. Twenty-four hours after cochlear perfusion with D-ASP, labeled neurons were observed in the ipsilateral, and to a much lesser extent in the contralateral, lateral superior olivary nucleus (LSO). The cells were small, primarily fusiform, and showed fewer synaptic contacts than other LSO cells. Combined transport of D-ASP and horseradish peroxidase indicated that all olivocochlear neurons within the LSO that projected to the injected cochlea were labeled by D-ASP. Labeled fibers coursed dorsally from the LSO, joined contralateral fibers that had passed under the floor of the fourth ventricle, and entered the VIIIth nerve root at its ventromedial edge. Adjacent to the ventral cochlear nucleus (VCN), densely labeled collateral fibers crossed the nerve root to enter the VCN. Labeled fibers and terminals were prominent in the central VCN. Neither retrograde transport of D-ASP by medial olivocochlear and vestibular efferents nor anterograde transport by VIIIth nerve afferents was observed. The D-ASP-labeled cells and fibers are clearly lateral olivocochlear efferents. Retrograde transport of D-ASP thus allows the cells, axons, and collaterals of the lateral olivocochlear system to be studied, morphologically, in isolation from other cells that project to the cochlea. Since the olivocochlear neurons are almost certainly cholinergic, retrograde amino acid transport does not necessarily identify the primary neurotransmitter of a neuron. Rather, it indicates the presence of selective uptake by the processes of that neuron at the site of amino acid injection

  19. Reduction of 3-methoxytyramine concentrations in the caudate nucleus of rats after exposure to high-energy iron particles: evidence for deficits in dopaminergic neurons

    International Nuclear Information System (INIS)

    Hunt, W.A.; Dalton, T.K.; Joseph, J.A.; Rabin, B.M.

    1990-01-01

    Exposure to low doses of high-energy iron particles can alter motor behavior. The ability of rats to hang from a wire has been reported to be significantly degraded after exposure to doses as low as 0.5 Gy. In addition, deficits in the ability of acetylcholine to regulate dopamine release in the caudate nucleus (an area in the brain important for motor function) have been found. The concentrations of 3-methoxytyramine (3-MT), a metabolite of dopamine whose concentrations reflect dopamine release in vivo, were measured after rats were exposed to different doses of high-energy iron particles to gain further information about the effect of radiation on the dopaminergic system. Concentrations of 3-MT were significantly reduced 3 days after exposure to 5 Gy but returned to control values by 8 days. After 6 months, concentrations were again less than control values. Exposure to 5 Gy of high-energy electrons or gamma photons had no effect 3 days after exposure. Very high doses of electrons were needed to alter 3-MT concentrations. One hundred grays of electrons decreased 3-MT 30 min after irradiation but levels returned to control values by 60 min. Gamma photons had no effect after doses up to 200 Gy. These results provide further evidence that exposure to heavy particles can degrade motor behavior through an action on dopaminergic mechanisms and that this can occur after doses much lower than those needed for low-LET radiation

  20. Dopamine in the Auditory Brainstem and Midbrain: Co-localization with Amino Acid Neurotransmitters and Gene Expression following Cochlear Trauma

    Directory of Open Access Journals (Sweden)

    Avril Genene eHolt

    2015-07-01

    Full Text Available Dopamine (DA modulates the effects of amino acid neurotransmitters, including GABA and glutamate, in motor, visual, olfactory and reward systems (Hnasko et al., 2010; Stuber et al., 2010; Hnasko and Edwards, 2012. The results suggest that DA may play a similar modulatory role in the auditory pathways. Previous studies have shown that deafness results in decreased GABA release, changes in excitatory neurotransmitter levels, and increased spontaneous neuronal activity within brainstem regions related to auditory function. Modulation of the expression and localization of tyrosine hydroxylase (TH; the rate limiting enzyme in the production of DA in the IC following cochlear trauma has been previously reported (Tong et al., 2005. In the current study the possibility of co-localization of TH with amino acid neurotransmitters (AANs was examined. Changes in the gene expression of TH were compared with changes in the gene expression of markers for AANs in the cochlear nucleus (CN and IC to determine whether those deafness related changes occur concurrently. The results indicate that bilateral cochlear ablation significantly reduced TH gene expression in the CN after two months while in the IC the reduction in TH was observed at both three days and two months following ablation. Furthermore, in the CN, glycine transporter 2 (GlyT2 and the GABA transporter (GABAtp were also significantly reduced only after two months. However, in the IC, DA receptor 1 (DRDA1, vesicular glutamate transporters 2 and 3 (vGluT2, vGluT3, GABAtp and GAD67 were reduced in expression both at the three day and two month time points. A close relationship between the distribution of TH and several of the AANs was determined in both the CN and the IC. In addition, GlyT2 and vGluT3 each co-localized with TH within IC somata and dendrites. Therefore, the results of the current study suggest that DA is spatially well positioned to influence the effects of AANs on auditory neurons.

  1. Nucleus-nucleus total reaction cross sections

    International Nuclear Information System (INIS)

    DeVries, R.M.; Peng, J.C.

    1980-01-01

    We compare sigma/sub R/(E) for nucleus-nucleus systems (obtained from existing direct measurements and derived from elastic scattering data) with nucleon-nucleon and nucleon-nucleus data. The energy dependence of sigma/sub R/(E) for nucleus-nucleus systems is found to be quite rapid; there appears to be no evidence for an energy independent, geometric sigma/sub R/. Simple parameter free microscopic calculations are able to quantitatively reproduce the data and thus, emphasize the dominance of nucleon-nucleon interactions in medium energy nucleus-nucleus collisions

  2. Cochlear implants in Waardenburg syndrome.

    Science.gov (United States)

    Cullen, Robert D; Zdanski, Carlton; Roush, Patricia; Brown, Carolyn; Teagle, Holly; Pillsbury, Harold C; Buchman, Craig

    2006-07-01

    Waardenburg syndrome is an autosomal-dominant syndrome characterized by dystopia canthorum, hyperplasia of the eyebrows, heterochromia irides, a white forelock, and sensorineural hearing loss in 20% to 55% of patients. This patient population accounts for approximately 2% of congenitally deaf children. The purpose of this retrospective case review was to describe the outcomes for those children with Waardenburg syndrome who have undergone cochlear implantation. Pediatric cochlear implant recipients with documented evidence of Waardenburg syndrome underwent retrospective case review. All patients received their cochlear implants at the study institution followed by outpatient auditory habilitation. Charts were reviewed for etiology and duration of deafness, age at time of cochlear implantation, perioperative complications, duration of use, and performance outcomes. Results of standard tests batteries for speech perception and production administered as a part of the patients' auditory habilitation were reviewed. Seven patients with Waardenburg syndrome and cochlear implants were identified. The average age at implantation was 37 months (range, 18-64 months) and the average duration of use was 69 months (range, 12-143 months). All of these patients are active users of their devices and perform very well after implantation. There were no major complications in this small group of patients. Children with congenital sensorineural hearing loss without other comorbidities (e.g., developmental delay, inner ear malformations) perform well when they receive cochlear implantation and auditory habilitation. Patients with Waardenburg syndrome can be expected to have above-average performance after cochlear implantation.

  3. Audiological outcomes of cochlear implantation in Waardenburg Syndrome

    Directory of Open Access Journals (Sweden)

    Magalhães, Ana Tereza de Matos

    2014-01-01

    Full Text Available Introduction: The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss. Aim: To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations. Method: This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed. Results: During this period, 806 patients received a cochlear implant and 10 of these (1.2% were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24® implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor. Conclusion: Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception.

  4. Audiological outcomes of cochlear implantation in Waardenburg Syndrome.

    Science.gov (United States)

    Magalhães, Ana Tereza de Matos; Samuel, Paola Angélica; Goffi-Gomez, Maria Valeria Schimdt; Tsuji, Robinson Koji; Brito, Rubens; Bento, Ricardo Ferreira

    2013-07-01

     The most relevant clinical symptom in Waardenburg syndrome is profound bilateral sensorioneural hearing loss.  To characterize and describe hearing outcomes after cochlear implantation in patients with Waardenburg syndrome to improve preoperative expectations.  This was an observational and retrospective study of a series of cases. Children who were diagnosed with Waardenburg syndrome and who received a multichannel cochlear implant between March 1999 and July 2012 were included in the study. Intraoperative neural response telemetry, hearing evaluation, speech perception, and speech production data before and after surgery were assessed.  During this period, 806 patients received a cochlear implant and 10 of these (1.2%) were diagnosed with Waardenburg syndrome. Eight of the children received a Nucleus 24(®) implant and 1 child and 1 adult received a DigiSonic SP implant. The mean age at implantation was 44 months among the children. The average duration of use of a cochlear implant at the time of the study was 43 months. Intraoperative neural responses were present in all cases. Patients who could use the speech processor effectively had a pure tone average of 31 dB in free-field conditions. In addition, the MUSS and MAIS questionnaires revealed improvements in speech perception and production. Four patients did not have a good outcome, which might have been associated with ineffective use of the speech processor.  Despite the heterogeneity of the group, patients with Waardenburg syndrome who received cochlear implants were found to have hearing thresholds that allowed access to speech sounds. However, patients who received early intervention and rehabilitation showed better evolution of auditory perception.

  5. Fourth ventricle injection of ghrelin decreases angiotensin II-induced fluid intake and neuronal activation in the paraventricular nucleus of the hypothalamus.

    Science.gov (United States)

    Plyler, Kimberly S; Daniels, Derek

    2017-09-01

    Ghrelin acts in the CNS to decrease fluid intake under a variety of dipsogenic and natriorexigenic conditions. Previous studies on this topic, however, focused on the forebrain as a site of action for this effect of ghrelin. Because the hindbrain contains neural substrates that are capable of mediating the well-established orexigenic effects of ghrelin, the current study tested the hypothesis that ghrelin applied to the hindbrain also would affect fluid intake. To this end, water and saline intakes were stimulated by central injection of angiotensin II (AngII) in rats that also received injections of ghrelin (0.5μg/μl) into either the lateral or fourth ventricle. Ghrelin injected into either ventricle reduced both water and 1.8% NaCl intake that was stimulated by AngII. The nature of the intake effect revealed some differences between the injection sites. For example, forebrain application of ghrelin reduced saline intake by a reduction in both the number of licking bursts and the size of each licking burst, but hindbrain application of ghrelin had a more selective effect on burst number. In an attempt to elucidate a brain structure in which hindbrain-administered ghrelin and forebrain-administered AngII interact to cause the ingestive response, we used Fos-immunohistochemistry in rats given the treatments used in the behavioral experiments. Although several brain areas were found to respond to either ghrelin or AngII, of the sites examined, only the paraventricular nucleus of the hypothalamus (PVN) emerged as a potential site of interaction. Specifically, AngII treatment caused expression of Fos in the PVN that was attenuated by concomitant treatment with ghrelin. These experiments provide the novel finding that the hindbrain contains elements that can respond to ghrelin and cause decreases in AngII-induced fluid intake, and that direct actions by ghrelin on forebrain structures is not necessary. Moreover, these studies suggest that the PVN is an important site

  6. COCHLEAR IMPLANTATION PREVALENCE IN ELDERLY

    Directory of Open Access Journals (Sweden)

    A. V. Starokha

    2014-01-01

    Full Text Available Current paper describes an experience of cochlear implantation in elderly. Cochlear implantation has become a widely accepted intervention in the treatment of individuals with severe-to-profound sensorineural hearing loss. Cochlear implants are now accepted as a standard of care to optimize hearing and subsequent speech development in children and adults with deafness. But cochlear implantation affects not only hearing abilities, speech perception and speech production; it also has an outstanding impact on the social life, activities and self-esteem of each patient. The aim of this study was to evaluate the cochlear implantation efficacy in elderly with severe to profound sensorineural hearing loss. There were 5 patients under our observation. Surgery was performed according to traditional posterior tympanotomy and cochleostomy for cochlear implant electrode insertion for all observed patients. The study was conducted in two stages: before speech processor’s activation and 3 months later. Pure tone free field audiometry was performed to each patient to assess the efficiency of cochlear implantation in dynamics. The aim of the study was also to evaluate quality of life in elderly with severe to profound sensorineural hearing loss after unilateral cochlear implantation. Each patient underwent questioning with 36 Item Short Form Health Survey (SF-36. SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The eight sections are: physical functioning; physical role functioning; emotional role functioning; vitality; emotional well-being; social role functioning; bodily pain; general health perceptions. Our results demonstrate that cochlear implantation in elderly consistently improved quality of life

  7. Labyrinthectomy with cochlear implantation.

    Science.gov (United States)

    Zwolan, T A; Shepard, N T; Niparko, J K

    1993-05-01

    Numerous reports indicate that the cochlea remains responsive to electrical stimulation following labyrinthectomy. We report a case of a 47-year-old woman with a severe to profound sensorineural hearing loss from birth, who developed episodic vertigo with symptoms suggestive of delayed onset endolymphatic hydrops. Following 8 months of failed medical and vestibular rehabilitation management, a right-sided labyrinthectomy combined with cochlear implantation was performed without complication. Postoperatively the patient was free of vertigo. Attempts to activate the patient's device between 4 to 12 weeks after surgery were unsuccessful as stimulation of the electrodes resulted in discomfort. However, all 20 electrodes elicited comfortable hearing sensations 16 weeks postsurgery. One year after the successful activation, the patient demonstrated improved sound awareness and speech recognition with the implant when compared with preoperative performance with a hearing aid. This case study suggests that electrical detection thresholds with prosthetic stimulation may be unstable in the recently labyrinthectomized ear but supports and extends prior observations of preserved cochlear responsiveness after labyrinthectomy.

  8. Cochlear implants and medical tourism.

    Science.gov (United States)

    McKinnon, Brian J; Bhatt, Nishant

    2010-09-01

    To compare the costs of medical tourism in cochlear implant surgery performed in India as compared to the United States. In addition, the cost savings of obtaining cochlear implant surgery in India were compare d to those of other surgical interventions obtained as a medical tourist. Searches were conducted on Medline and Google using the search terms: 'medical tourism', 'medical offshoring', 'medical outsourcing', 'cochlear implants' and 'cochlear implantation'. The information regarding cost of medical treatment was obtained from personal communication with individuals familiar with India's cochlear implantation medical tourism industry. The range of cost depended on length of stay as well as the device chosen. Generally the cost, inclusive of travel, surgery and device, was in the range of $21,000-30,000, as compared to a cost range of $40,000-$60,000 in the US. With the escalating cost of healthcare in the United States, it is not surprising that some patients would seek to obtain surgical care overseas at a fraction of the cost. Participants in medical tourism often have financial resources, but lack health insurance coverage. While cardiovascular and orthopedic surgery performed outside the United States in India at centers that cater to medical tourists are often performed at one-quarter to one-third of the cost that would have been paid in the United States, the cost differential for cochlear implants is not nearly as favorable.

  9. Ototoxicity of paclitaxel in rat cochlear organotypic cultures

    International Nuclear Information System (INIS)

    Dong, Yang; Ding, Dalian; Jiang, Haiyan; Shi, Jian-rong; Salvi, Richard; Roth, Jerome A.

    2014-01-01

    Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons

  10. Ototoxicity of paclitaxel in rat cochlear organotypic cultures

    Energy Technology Data Exchange (ETDEWEB)

    Dong, Yang [Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Ding, Dalian; Jiang, Haiyan [Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Shi, Jian-rong [Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China); Salvi, Richard [Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States); Roth, Jerome A., E-mail: jaroth@buffalo.edu [Department of Pharmacology and Toxicology, University at Buffalo, NY 14214 (United States)

    2014-11-01

    Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons.

  11. Persistent Thalamic Sound Processing Despite Profound Cochlear Denervation

    Directory of Open Access Journals (Sweden)

    Anna R. Chambers

    2016-08-01

    Full Text Available Neurons at higher stages of sensory processing can partially compensate for a sudden drop in input from the periphery through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where > 95% of synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore the cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, cortical processing and perception recover despite the absence of an auditory brainstem response (ABR or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC, an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the auditory cortex (ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB of awake mice. Sound-driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory

  12. Congenitally Deafblind Children and Cochlear Implants

    DEFF Research Database (Denmark)

    Dammeyer, Jesper Herup

    2008-01-01

    There has been much research conducted demonstrating the positive benefits of cochlear implantation (CI) in children who are deaf. Research on cochlear implantation in children who are both deaf and blind, however, is lacking. The purpose of this article is to present a study of 5 congenitally...... deafblind children who received cochlear implants between 2.2 and 4.2 years of age.  Ratings of video observations were used to measure the children's early communication development with and without the use of their cochlear implants. In addition, parental interviews were used to assess the benefits...... parents perceived regarding their children's cochlear implants. Two examples are included in this article to illustrate the parents' perspectives about cochlear implantation in their deafblind children. Benefits of cochlear implantation in this cohort of children included improved attention and emotional...

  13. [Bilateral cochlear implants].

    Science.gov (United States)

    Müller, J

    2017-07-01

    Cochlear implants (CI) are standard for the hearing rehabilitation of severe to profound deafness. Nowadays, if bilaterally indicated, bilateral implantation is usually recommended (in accordance with German guidelines). Bilateral implantation enables better speech discrimination in quiet and in noise, and restores directional and spatial hearing. Children with bilateral CI are able to undergo hearing-based hearing and speech development. Within the scope of their individual possibilities, bilaterally implanted children develop faster than children with unilateral CI and attain, e.g., a larger vocabulary within a certain time interval. Only bilateral implantation allows "binaural hearing," with all the benefits that people with normal hearing profit from, namely: better speech discrimination in quiet and in noise, as well as directional and spatial hearing. Naturally, the developments take time. Binaural CI users benefit from the same effects as normal hearing persons: head shadow effect, squelch effect, and summation and redundancy effects. Sequential CI fitting is not necessarily disadvantageous-both simultaneously and sequentially fitted patients benefit in a similar way. For children, earliest possible fitting and shortest possible interval between the two surgeries seems to positively influence the outcome if bilateral CI are indicated.

  14. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    OpenAIRE

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-01-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connecti...

  15. Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels☆

    Science.gov (United States)

    Xie, Joanna; Pak, Kwang; Evans, Amaretta; Kamgar-Parsi, Andy; Fausti, Stephen; Mullen, Lina; Ryan, Allen Frederic

    2013-01-01

    The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant. PMID:24459465

  16. Nucleus retroambiguus projections to the periaqueductal gray in the cat

    NARCIS (Netherlands)

    Klop, EM; Mouton, LJ; Holstege, G

    2002-01-01

    The nucleus retroambiguus (NRA) of the caudal medulla is a relay nucleus by which neurons of the mesencephalic periaqueductal gray (PAG) reach motoneurons of pharynx, larynx, soft palate, intercostal and abdominal muscles, and several muscles of the hindlimbs. These PAG-NRA-motoneuronal projections

  17. Psychoacoustic Performance and Music and Speech Perception in Prelingually Deafened Children with Cochlear Implants

    OpenAIRE

    Jung, Kyu Hwan; Won, Jong Ho; Drennan, Ward R.; Jameyson, Elyse; Miyasaki, Gary; Norton, Susan J.; Rubinstein, Jay T.

    2012-01-01

    The number of pediatric cochlear implant (CI) recipients has increased substantially over the past 10 years, and it has become more important to understand the underlying mechanisms of the variable outcomes in this population. In this study, psychoacoustic measures of spectral-ripple and Schroeder-phase discrimination, the Clinical Assessment of Music Perception, and consonant-nucleus-consonant (CNC) word recognition in quiet and spondee reception threshold (SRT) in noise tests have been pres...

  18. Design of a new electrode array for cochlear implants

    International Nuclear Information System (INIS)

    Kha, H.; Chen, B.

    2010-01-01

    Full text: This study aims to design a new electrode array which can be precisely located beneath the basilar membrane within the cochlear scala tympani. This placement of the electrode array is beneficial for increasing the effectiveness of the electrical stimulation of the audi tory nerves and maximising the growth factors delivered into the cochlea for regenerating the progressively lost auditory neurons, thereby significantly improving performance of the cochlear implant systems. Methods The design process involved two steps. First, the biocom patible nitinol-based shape memory alloy, of which mechanical deformation can be controlled using electrical cUTents/fields act vated by body temperature, was selected. Second, five different designs of the electrode array with embedded nitinol actuators were studied (Table I). The finite element method was employed to predict final positions of these electrode arrays. Results The electrode array with three 6 mm actuators at 2-8, 8-J4 and 14-20 mm from the tip (Fig. I) was found to be located most closely to the basilar membrane, compared with those in the other four cases. Conclusions A new nitinol cochlear implant electrode array with three embedded nitinol actuators has been designed. This electrode array is expected to be located beneath the basilar membrane for maximising the delivery of growth factors. Future research will involve the manufacturing of a prototype of this electrode array for use in insertion experiments and neurotrophin release tests.

  19. Neuronal spike-train responses in the presence of threshold noise.

    Science.gov (United States)

    Coombes, S; Thul, R; Laudanski, J; Palmer, A R; Sumner, C J

    2011-03-01

    The variability of neuronal firing has been an intense topic of study for many years. From a modelling perspective it has often been studied in conductance based spiking models with the use of additive or multiplicative noise terms to represent channel fluctuations or the stochastic nature of neurotransmitter release. Here we propose an alternative approach using a simple leaky integrate-and-fire model with a noisy threshold. Initially, we develop a mathematical treatment of the neuronal response to periodic forcing using tools from linear response theory and use this to highlight how a noisy threshold can enhance downstream signal reconstruction. We further develop a more general framework for understanding the responses to large amplitude forcing based on a calculation of first passage times. This is ideally suited to understanding stochastic mode-locking, for which we numerically determine the Arnol'd tongue structure. An examination of data from regularly firing stellate neurons within the ventral cochlear nucleus, responding to sinusoidally amplitude modulated pure tones, shows tongue structures consistent with these predictions and highlights that stochastic, as opposed to deterministic, mode-locking is utilised at the level of the single stellate cell to faithfully encode periodic stimuli.

  20. Reading skills after cochlear implantation

    NARCIS (Netherlands)

    Vermeulen, A.M.

    2007-01-01

    It has frequently been found that profoundly deaf children with conventional hearing aids have difficulties with the comprehension of written text. Cochlear Implants (CIs) were expected to enhance the reading comprehension of these profoundly deaf children because they provide auditory access to

  1. Advancing Binaural Cochlear Implant Technology

    Directory of Open Access Journals (Sweden)

    Mathias Dietz

    2015-12-01

    Full Text Available This special issue contains a collection of 13 papers highlighting the collaborative research and engineering project entitled Advancing Binaural Cochlear Implant Technology—ABCIT—as well as research spin-offs from the project. In this introductory editorial, a brief history of the project is provided, alongside an overview of the studies.

  2. Perspective of ultrarelativistic nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Specht, H.J.

    1985-01-01

    The paper concerns the lectures given at the International School of nuclear physics, Erice, 1985, which survey the expectations for the field of ultrarelativistic nucleus-nucleus collisions. The primary motivation for the field, the organization of the lectures, and a description of the NA 34 experiment, are all briefly given. (U.K.)

  3. Modifying cochlear implant design: advantages of placing a return electrode in the modiolus.

    Science.gov (United States)

    Ho, Steven Y; Wiet, Richard J; Richter, Claus-Peter

    2004-07-01

    A modiolar return electrode significantly increases the current flow across spiral ganglion cells into the modiolus, and may decrease the cochlear implant's power requirements. Ideal cochlear implants should maximize current flow into the modiolus to stimulate auditory neurons. Previous efforts to facilitate current flow through the modiolus included the fabrication and use of precurved electrodes designed to "hug" the modiolus and silastic positioners designed to place the electrodes closer to the modiolus. In contrast to earlier efforts, this study explores the effects of return electrode placement on current distributions in the modiolus. The effects of return electrode positioning on current flow in the modiolus were studied in a Plexiglas model of the cochlea. Results of model measurements were confirmed by measurements in the modiolus of human temporal bones. The return electrode was placed either within the modiolus, or remotely, outside the temporal bone, simulating contemporary cochlear implant configurations using monopolar stimulation. Cochlear model results clearly show that modiolar current amplitudes can be influenced significantly by the location of the return electrode, being larger when placed into the modiolus. Temporal bone data show similar findings. Voltages recorded in the modiolus are, on average, 2.8 times higher with the return electrode in the modiolus compared with return electrode locations outside the temporal bone. Placing a cochlear implant's return electrode in the modiolus should significantly reduce its power consumption. Reducing power requirements should lead to improved efficiency, safer long-term use, and longer device life.

  4. Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue.

    Science.gov (United States)

    Viana, Lucas M; O'Malley, Jennifer T; Burgess, Barbara J; Jones, Dianne D; Oliveira, Carlos A C P; Santos, Felipe; Merchant, Saumil N; Liberman, Leslie D; Liberman, M Charles

    2015-09-01

    Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina. Quantitative analysis of five "normal" ears, aged 54-89 yrs, without any history of otologic disease, suggests that cochlear synaptopathy and the degeneration of cochlear nerve peripheral axons, despite a near-normal hair cell population, may be an important component of human presbycusis. Although primary cochlear nerve degeneration is not expected to affect audiometric thresholds, it may be key to problems with hearing in noise that are characteristic of declining hearing abilities in the aging ear. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. High energy nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Bhalla, K.B.

    1980-01-01

    An attempt is made to explain nucleus-nucleus collisions based on nuclear emulsion experiments. Peripheral and central collisions are described in detail. Assuming the fireball model, the concepts of geometry, kinematics and thermodynamics in this model are discussed. Projectile and target fragmentations are studied. The advantages of using nuclear emulsions as detectors, are mentioned. Proton-nucleus collisions and nucleus-nucleus collisions are compared. Interactions, of projectiles such as Ca, B and C on targets such as Pb, Ag, Br etc. at very high energies (approximately 300 to 1700 Gev) are listed. A comparison of the near multiplicities in these interactions is given. A generalized explanation is given on the processes involved in these interactions. (A.K.)

  6. [Cochlear implant treatment in Germany].

    Science.gov (United States)

    Jacob, R; Stelzig, Y

    2013-01-01

    Restoration of impaired auditory function through cochlear implant is possible, with high reliably and great success. Nevertheless, there are regular disputes between patients and insurance companies due to high costs. In Germany, approx. 1.9 Mio. people are severely hearing impaired. It can be estimated that for adequate hearing rehabilitation about 30,000 cochlear implants/year are necessary. Currently, less than 10% of those affected are offered cochlear implant. A handicap is defined if there is deviation from normal hearing for more than 6 months. This sets a time frame for the supply with cochlear implant after sudden deafness. The professional code requires to advice all medical options to a person seeking help for hearing loss. This includes benefit-risk consideration. At this point, the economic aspect plays no role. The indication for medical treatment is only subject to the treating physician and should not be modified by non-physicians or organizations. It should be noted that a supply of hearing aids is qualitatively different to the help from a cochlear implant, which provides a restoration of lost function. In social law (SGB V and IX) doctors are requested to advise and recommend all measures which contribute to normal hearing (both sides). This indicates that doctors may be prosecuted for not offering help when medically possible, just because health insurance employees did not approve the cost balance. The current situation, with insufficient medical care for the hearing impaired, needs clarifying. To do this, patients, health insurance companies, the political institutions, legislation and professional societies need to accept their responsibilities.

  7. Diversity in cochlear morphology and its influence on cochlear implant electrode position

    NARCIS (Netherlands)

    Marel, K.S. van der; Briaire, J.J.; Wolterbeek, R..; Snel-Bongers, J.; Verbist, B.M.; Frijns, J.H.

    2014-01-01

    To define a minimal set of descriptive parameters for cochlear morphology and study its influence on the cochlear implant electrode position in relation to surgical insertion distance.Cochlear morphology and electrode position were analyzed using multiplanar reconstructions of the pre- and

  8. The nucleus raphe interpositus in spinocerebellar ataxia type 3 (Machado-Joseph disease)

    NARCIS (Netherlands)

    Rub, U; Brunt, ER; Gierga, K; Schultz, C; Paulson, H; de Vos, RAI; Braak, H

    The nucleus raphe interpositus (RIP) plays an important role in the premotor network for saccades. Its omnipause neurons gate the activity of the burst neurons for vertical saccades lying within the rostral interstitial nucleus of the medial longitudinal fascicle and that for horizontal saccades

  9. Mechanisms contributing to cluster formation in the inferior olivary nucleus in brainstem slices from postnatal mice

    DEFF Research Database (Denmark)

    Kølvraa, Mathias; Müller, Felix C; Jahnsen, Henrik

    2014-01-01

    The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5-P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve as a synch......The inferior olivary nucleus (IO) in in vitro slices from postnatal mice (P5.5-P15.5) spontaneously generates clusters of neurons with synchronous calcium transients, and intracellular recordings from IO neurons suggest that electrical coupling between neighbouring IO neurons may serve...

  10. Preservation of the nucleus X-pelvic floor motosystem in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

    Schrøder, H D; Reske-Nielsen, E

    1984-01-01

    to the neuropathological findings, and the observations are compared with previous neuropathological studies concerning Onuf's nucleus X as well with experimental studies including this nucleus. It is pointed out that structural and biochemical differences must exist between nucleus X neurons and other motoneurons....

  11. Cochlear implant revision surgeries in children.

    Science.gov (United States)

    Amaral, Maria Stella Arantes do; Reis, Ana Cláudia Mirândola B; Massuda, Eduardo T; Hyppolito, Miguel Angelo

    2018-02-16

    The surgery during which the cochlear implant internal device is implanted is not entirely free of risks and may produce problems that will require revision surgeries. To verify the indications for cochlear implantation revision surgery for the cochlear implant internal device, its effectiveness and its correlation with certain variables related to language and hearing. A retrospective study of patients under 18 years submitted to cochlear implant Surgery from 2004 to 2015 in a public hospital in Brazil. Data collected were: age at the time of implantation, gender, etiology of the hearing loss, audiological and oral language characteristics of each patient before and after Cochlear Implant surgery and any need for surgical revision and the reason for it. Two hundred and sixty-five surgeries were performed in 236 patients. Eight patients received a bilateral cochlear implant and 10 patients required revision surgery. Thirty-two surgeries were necessary for these 10 children (1 bilateral cochlear implant), of which 21 were revision surgeries. In 2 children, cochlear implant removal was necessary, without reimplantation, one with cochlear malformation due to incomplete partition type I and another due to trauma. With respect to the cause for revision surgery, of the 8 children who were successfully reimplanted, four had cochlear calcification following meningitis, one followed trauma, one exhibited a facial nerve malformation, one experienced a failure of the cochlear implant internal device and one revision surgery was necessary because the electrode was twisted. The incidence of the cochlear implant revision surgery was 4.23%. The period following the revision surgeries revealed an improvement in the subject's hearing and language performance, indicating that these surgeries are valid in most cases. Copyright © 2018 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  12. Recognition of "real-world" musical excerpts by cochlear implant recipients and normal-hearing adults.

    Science.gov (United States)

    Gfeller, Kate; Olszewski, Carol; Rychener, Marly; Sena, Kimberly; Knutson, John F; Witt, Shelley; Macpherson, Beth

    2005-06-01

    The purposes of this study were (a) to compare recognition of "real-world" music excerpts by postlingually deafened adults using cochlear implants and normal-hearing adults; (b) to compare the performance of cochlear implant recipients using different devices and processing strategies; and (c) to examine the variability among implant recipients in recognition of musical selections in relation to performance on speech perception tests, performance on cognitive tests, and demographic variables. Seventy-nine cochlear implant users and 30 normal-hearing adults were tested on open-set recognition of systematically selected excerpts from musical recordings heard in real life. The recognition accuracy of the two groups was compared for three musical genre: classical, country, and pop. Recognition accuracy was correlated with speech recognition scores, cognitive measures, and demographic measures, including musical background. Cochlear implant recipients were significantly less accurate in recognition of previously familiar (known before hearing loss) musical excerpts than normal-hearing adults (p genre. Implant recipients were most accurate in the recognition of country items and least accurate in the recognition of classical items. There were no significant differences among implant recipients due to implant type (Nucleus, Clarion, or Ineraid), or programming strategy (SPEAK, CIS, or ACE). For cochlear implant recipients, correlations between melody recognition and other measures were moderate to weak in strength; those with statistically significant correlations included age at time of testing (negatively correlated), performance on selected speech perception tests, and the amount of focused music listening following implantation. Current-day cochlear implants are not effective in transmitting several key structural features (i.e., pitch, harmony, timbral blends) of music essential to open-set recognition of well-known musical selections. Consequently, implant

  13. Pion production in nucleus--nucleus collisions

    International Nuclear Information System (INIS)

    Schroeder, L.S.

    1975-06-01

    Current work on pion production in high-energy nucleus-nucleus collisions is reviewed. The majority of existing data are of the inclusive variety in which a single final state pion is detected. Experimental data are compared and their possible contributions to obtaining new information on nuclear structure is discussed. Various models which attempt to explain the observed single-inclusive-pion spectra either on the basis of a nucleon-nucleus interaction in which Fermi motion is included or on some type of cooperative model are examined. Other areas of interest involving pion production include tests of charge symmetry and pion multiplicities. (9 figures, 1 table) (U.S.)

  14. CT evaluation of preoperative cochlear implantation cochlear implantation

    International Nuclear Information System (INIS)

    Tan Xiuzhong; Zhong Lansheng; Lan Bowen; Huang Yaosheng; Du Baowen; Zhu Jian

    2004-01-01

    Objective: To evaluate CT scan as a preoperative evaluation for cochlear implantation candidates. Methods: Axial high-resolution temporal bone CT and three-dimensional reconstruction of inner ear were performed in 93 patients with sensorineural hearing loss. results: Among 81 patients with congenital sensorineural deafness, Mondini malformation was seen in 7 case (13 ears); large vestibular aqueduct syndrome (LVAS) was revealed in 5 cases (8 ears); and inner ear ossification was found in 1 case (2 ears). In 1 case (2 ears) of inner ear fibrosis, reduced cochlear signal was noted on MRI but no unremarkable findings was shown on CT scan, however, in the operation, the device could not inserted into the basal circle of the cochlea, due to fibrous obliteration. In 12 patients with post-speech deafness, chronic suppurative tympanitis was seen in 2 cases (4 ears), and inner ear ossification was revealed in 1 case (2 ears). Conclusion: CT plays an indispensable role in the pre-operative evaluation of cochlear implantation. T 2 -weighted FSE-MRI of the inner ear is a useful complementary to CT scan. (authors)

  15. Hadron-nucleus collisions

    International Nuclear Information System (INIS)

    Strugalski, Z.

    1981-01-01

    Qualitative picture of high energy hadron-nucleus collision process, emerging from the analysis of experimental data, is presented. Appropriate description procedure giving a possibility of reproducing various characteristics of this process in terms of the data on elementary hadron-nucleon interaction is proposed. Formula reproducing hadron-nucleus collision cross sections is derived. Inelastic collision cross sections for pion-nucleus and proton-nucleus reactions at wide energy interval are calculated for Pb, Ag, and Al targets. A-dependence of cross sections for pion-nucleus and proton-nucleus collisions at nearly 50 GeV/c momentum were calculated and compared with existing experimental data. Energy dependence of cross sections for hadron-nucleus collisions is determined simply by energy dependence of corresponding cross sections for hadron-nucleon collisions; A-dependence is determined simply by nuclear sizes and nucleon density distributions in nuclei

  16. Microanatomy of the cochlear hook

    Science.gov (United States)

    Kwan, Changyow Claire; Tan, Xiaodong; Stock, Stuart R.; Soriano, Carmen; Xiao, Xianghui; Richter, Claus-Peter

    2017-09-01

    Communication among humans occurs through coding and decoding of acoustic information. The inner ear or cochlea acts as a frequency analyzer and divides the acoustic signal into small frequency bands, which are processed at different sites along the cochlea. The mechano-electrical conversion is accomplished by the soft tissue structures in the cochlea. While the anatomy for most of the cochlea has been well described, a detailed description of the very high frequency and vulnerable cochlear hook region is missing. To study the cochlear hook, mice cochleae were imaged with synchrotron radiation and high-resolution reconstructions have been made from the tomographic scans. This is the first detailed description of the bony and soft tissues of the hook region of the mammalian cochlea.

  17. "COCHLEAR IMPLANTATION IN PATIENTS WITH INNER EAR MALFORMATIONS"

    Directory of Open Access Journals (Sweden)

    P. Borghei S. Abdi

    2004-08-01

    Full Text Available Performing cochlear implantation in patients with inner ear malformation has always been a matter of dispute. This study was designed to analyze the operative findings,complications, and postoperative performance of patients with inner ear anomalies who underwent cochlear implantation. Six patients with inner ear malformations underwent implantation in our academic tertiary referral center from 1997 to 2002. The average follow-up period was 27 months. Malformations included one incomplete partition, one common cavity, one narrow internal acoustic canal (IAC in a patient with Riley-Day syndrome and 3 cases of large vestibular aqueduct. All received multi-channel implants either Nucleus 22 or Clarion device. Facial nerve was anomalous in 2 cases. CSF gusher occurred in 4 patients, which was controlled with packing the cochleostomy site. In all cases, the full length of electrode array was inserted, except one with Mondini's dysplasia where insertion failed in the first operation and was referred to another center for a successful surgery on the opposite ear. No other surgical complications were encountered. In 4 cases, all the 22 electrodes could be activated. All patients showed improved hearing performance after implantation. Four showed open-set speech recognition. The one with narrow IAC showed improved awareness to environmental sounds. In the other case (common cavity, the perception tests could not be performed because of very young age. Cochlear implantation in patients with inner ear malformations is a successful way of rehabilitation, although complications should be expected and auditory responses may be highly variable and relatively moderate.

  18. Nucleus-nucleus potential with repulsive core and elastic scattering. Part 1. Nucleus-nucleus interaction potential

    International Nuclear Information System (INIS)

    Davidovs'ka, O.Yi.; Denisov, V.Yu.; Nesterov, V.O.

    2010-01-01

    Various approaches for nucleus-nucleus interaction potential evaluation are discussed in details. It is shown that the antisymmetrization of nucleons belonging to different nuclei and the Pauli principle give the essential contribution into the nucleus-nucleus potential at distances, when nuclei are strongly overlapping, and lead to appearance of the repulsive core of nucleus nucleus interaction at small distances between nuclei.

  19. Antiproton production in nucleon-nucleus and nucleus-nucleus collisions at the CERN-SPS

    International Nuclear Information System (INIS)

    Kadija, K.; Schmitz, N.; Seyboth, P.

    1996-01-01

    A model for antiproton production in nucleon-nucleus and nucleus-nucleus collisions at 200 GeV per nucleon, based on the wounded nucleon model is developed. The predictions are compared to published nucleon-nucleus and sulphur-nucleus data. The results suggest the presence of similar antiproton production processes in nucleon-nucleus and nucleus-nucleus collisions near midrapidity. (orig.)

  20. Deafblind People's Experiences of Cochlear Implantation

    Science.gov (United States)

    Soper, Janet

    2006-01-01

    Cochlear implants are electronic devices that create the sensation of hearing in those who cannot obtain any benefit from conventional hearing aids. This article examines the experience of cochlear implantation in a select group of individuals with acquired deafblindness, focusing on three key themes: access to communication, information and…

  1. Effect of ghrelin receptor agonist and antagonist on the activity of arcuate nucleus tyrosine hydroxylase containing neurons in C57BL/6 male mice exposed to normal or high fat diet

    Czech Academy of Sciences Publication Activity Database

    Pirník, Z.; Majerčíková, Z.; Holubová, Martina; Pirník, R.; Železná, Blanka; Maletínská, Lenka; Kiss, A.

    2014-01-01

    Roč. 65, č. 4 (2014), s. 477-486 ISSN 0867-5910 Institutional support: RVO:61388963 Keywords : growth hormone secretagogue receptor * ghrelin receptor agonist * ghrelin receptor antagonist * high fat diet * tyrosine hydroxylase * arcuate nucleus * food intake Subject RIV: CE - Biochemistry Impact factor: 2.386, year: 2014

  2. Importance of cochlear health for implant function.

    Science.gov (United States)

    Pfingst, Bryan E; Zhou, Ning; Colesa, Deborah J; Watts, Melissa M; Strahl, Stefan B; Garadat, Soha N; Schvartz-Leyzac, Kara C; Budenz, Cameron L; Raphael, Yehoash; Zwolan, Teresa A

    2015-04-01

    Amazing progress has been made in providing useful hearing to hearing-impaired individuals using cochlear implants, but challenges remain. One such challenge is understanding the effects of partial degeneration of the auditory nerve, the target of cochlear implant stimulation. Here we review studies from our human and animal laboratories aimed at characterizing the health of the implanted cochlea and the auditory nerve. We use the data on cochlear and neural health to guide rehabilitation strategies. The data also motivate the development of tissue-engineering procedures to preserve or build a healthy cochlea and improve performance obtained by cochlear implant recipients or eventually replace the need for a cochlear implant. This article is part of a Special Issue entitled . Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Binaural Speech Understanding With Bilateral Cochlear Implants in Reverberation.

    Science.gov (United States)

    Kokkinakis, Kostas

    2018-03-08

    The purpose of this study was to investigate whether bilateral cochlear implant (CI) listeners who are fitted with clinical processors are able to benefit from binaural advantages under reverberant conditions. Another aim of this contribution was to determine whether the magnitude of each binaural advantage observed inside a highly reverberant environment differs significantly from the magnitude measured in a near-anechoic environment. Ten adults with postlingual deafness who are bilateral CI users fitted with either Nucleus 5 or Nucleus 6 clinical sound processors (Cochlear Corporation) participated in this study. Speech reception thresholds were measured in sound field and 2 different reverberation conditions (0.06 and 0.6 s) as a function of the listening condition (left, right, both) and the noise spatial location (left, front, right). The presence of the binaural effects of head-shadow, squelch, summation, and spatial release from masking in the 2 different reverberation conditions tested was determined using nonparametric statistical analysis. In the bilateral population tested, when the ambient reverberation time was equal to 0.6 s, results indicated strong positive effects of head-shadow and a weaker spatial release from masking advantage, whereas binaural squelch and summation contributed no statistically significant benefit to bilateral performance under this acoustic condition. These findings are consistent with those of previous studies, which have demonstrated that head-shadow yields the most pronounced advantage in noise. The finding that spatial release from masking produced little to almost no benefit in bilateral listeners is consistent with the hypothesis that additive reverberation degrades spatial cues and negatively affects binaural performance. The magnitude of 4 different binaural advantages was measured on the same group of bilateral CI subjects fitted with clinical processors in 2 different reverberation conditions. The results of this work

  4. K+-nucleus interaction

    International Nuclear Information System (INIS)

    Gibbs, W.R.

    1984-01-01

    The K + -nucleus system is reviewed and comparison with data is made. The principal conclusions are that the theoretical uncertainties in relating the K + -nucleus interaction to the K + -nucleon interaction are very small and hence the positive kaon makes an excellent probe of the nucleus. It is suggested that this particle may be more sensitive to non-nucleonic degrees of freedom (especially quarks) than classical probes

  5. [The evolution of surgical interventions for cochlear implantation at the Russian Research and Practical Centre of Audiology and Hearing Rehabilitation].

    Science.gov (United States)

    Fedoseev, V I; Dmitriev, N S

    2014-01-01

    The objective of the present study was to estimate and analyse the effectiveness and labour intensity of the methods of surgical intervention for cochlear implantation. The analysis of the surgical stage of cochlear implantation was based on the examination of 2073 children and adults during the period from 1991 to 2013. The age of the patients varied between 6 months to 71 years. The cause of deafness was meningitis and an injury in 11% and 6% of the patients respectively. The cochlear implants from Advanced Bionics were inserted in 495 patients, those from Med-El in 9 ones , and from Neurelec in 20, and Nucleus devices from Cochlear in the remaining patents (n=1549) including 37 double-array electrodes and a Hybrid implant for electroacoustic correction of hearing . The implants with a straight and perimodiolar electrode were placed in a roughly equal number of the patients. The rationale for the performance of selected components of the surgical stage of cochlear implantation was developed along with the technical procedures for the purpose applied at this Centre since 1991. The original methods for the fixation and covering of the receiver-stimulator and also for the choice of the place of the electrode array insertion into the cochlea are described. They allowed to significantly decrease the frequency of complications, duration and extent of the surgical intervention as well as to reduce to a minimum post-operative manipulations.

  6. Cochlear Implant Spatial Selectivity with Monopolar, Bipolar and Tripolar Stimulation

    Science.gov (United States)

    Zhu, Ziyan; Tang, Qing; Zeng, Fan-Gang; Guan, Tian; Ye, Datian

    2011-01-01

    Sharp spatial selectivity is critical to auditory performance, particularly in pitch related tasks. Most contemporary cochlear implants have employed monopolar stimulation that produces broad electric fields, which presumably contribute to poor pitch and pitch-related performance by implant users. Bipolar or tripolar stimulation can generate focused electric fields but requires higher current to reach threshold and, more interestingly, has not produced any apparent improvement in cochlear implant performance. The present study addressed this dilemma by measuring psychophysical and physiological spatial selectivity with both broad and focused stimulations in the same cohort of subjects. Different current levels were adjusted by systematically measuring loudness growth for each stimulus, each stimulation mode, and in each subject. Both psychophysical and physiological measures showed that, although focused stimulation produced significantly sharper spatial tuning than monopolar stimulation, it could shift the tuning position or even split the tuning tips. The altered tuning with focused stimulation is interpreted as a result of poor electrode-to-neuron interface in the cochlea, and is suggested to be mainly responsible for the lack of consistent improvement in implant performance. A linear model could satisfactorily quantify the psychophysical and physiological data and derive the tuning width. Significant correlation was found between the individual physiological and psychophysical tuning widths, and the correlation was improved by log-linearly transforming the physiological data to predict the psychophysical data. Because the physiological measure took only one-tenth of the time of the psychophysical measure, the present model is of high clinical significance in terms of predicting and improving cochlear implant performance. PMID:22138630

  7. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

    Science.gov (United States)

    Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

    2015-08-26

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the

  8. Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

    Science.gov (United States)

    Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

    2015-01-01

    Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping

  9. Audiovisual segregation in cochlear implant users.

    Directory of Open Access Journals (Sweden)

    Simon Landry

    Full Text Available It has traditionally been assumed that cochlear implant users de facto perform atypically in audiovisual tasks. However, a recent study that combined an auditory task with visual distractors suggests that only those cochlear implant users that are not proficient at recognizing speech sounds might show abnormal audiovisual interactions. The present study aims at reinforcing this notion by investigating the audiovisual segregation abilities of cochlear implant users in a visual task with auditory distractors. Speechreading was assessed in two groups of cochlear implant users (proficient and non-proficient at sound recognition, as well as in normal controls. A visual speech recognition task (i.e. speechreading was administered either in silence or in combination with three types of auditory distractors: i noise ii reverse speech sound and iii non-altered speech sound. Cochlear implant users proficient at speech recognition performed like normal controls in all conditions, whereas non-proficient users showed significantly different audiovisual segregation patterns in both speech conditions. These results confirm that normal-like audiovisual segregation is possible in highly skilled cochlear implant users and, consequently, that proficient and non-proficient CI users cannot be lumped into a single group. This important feature must be taken into account in further studies of audiovisual interactions in cochlear implant users.

  10. Microscopic model of nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Harvey, B.G.

    1986-04-01

    The collision of two nuclei is treated as a collection of collisions between the nucleons of the projectile and those of the target nucleus. The primary projectile fragments contain only those nucleons that did not undergo a collision. The inclusive and coincidence cross sections result from the decay of the excited primary fragments. 15 refs., 5 figs

  11. Assessment of Cochlear Function during Cochlear Implantation by Extra- and Intracochlear Electrocochleography

    OpenAIRE

    Dalbert, Adrian; Pfiffner, Flurin; Hoesli, Marco; Koka, Kanthaiah; Veraguth, Dorothe; Roosli, Christof; Huber, Alexander

    2018-01-01

    Objective: The aims of this study were: (1) To investigate the correlation between electrophysiological changes during cochlear implantation and postoperative hearing loss, and (2) to detect the time points that electrophysiological changes occur during cochlear implantation. Material and Methods: Extra- and intracochlear electrocochleography (ECoG) were used to detect electrophysiological changes during cochlear implantation. Extracochlear ECoG recordings were conducted through a needle elec...

  12. Prevention and management of cochlear implant infections.

    Science.gov (United States)

    Gluth, Michael B; Singh, Rajesh; Atlas, Marcus D

    2011-11-01

    Understanding the issues of infection related to an implantable medical device is crucial to all cochlear implant teams. Furthermore, given the risk of central nervous system complications and the relatively high quantity of underlying resource investment associated with cochlear implantation, the stakes of infection are high. The optimal strategies to prevent and manage such infections are still evolving as good-quality prospective data to guide such management decisions are not yet abundant within the medical literature and many recommendations are based on retrospective reviews or anecdotal evidence. We will outline a general strategy to deal with cochlear implant-related infection based on both the authors' experience and the published literature.

  13. Endorphinic neurons are contacting the tuberoinfundibular dopaminergic neurons in the rat brain

    International Nuclear Information System (INIS)

    Morel, G.; Pelletier, G.

    1986-01-01

    The anatomical relationships between endorphinic neurons and dopaminergic neurons were evaluated in the rat hypothalamus using a combination of immunocytochemistry and autoradiography. In the arcuate nucleus, endorphinic endings were seen making contacts with dopaminergic cell bodies and dendrites. No synapsis could be observed at the sites of contacts. These results strongly suggest that the endorphinic neurons are directly acting on dopaminergic neurons to modify the release of dopamine into the pituitary portal system

  14. Is All Human Hearing Cochlear?

    Directory of Open Access Journals (Sweden)

    Seyede Faranak Emami

    2013-01-01

    Full Text Available The objective of this cross-sectional study was to investigate the possibility that the saccule may contribute to human hearing. The forty participants included twenty healthy people and twenty other subjects selected from patients who presented with benign paroxysmal positional vertigo to Audiology Department of Hazrat Rasoul Akram hospital (Tehran, Iran. Assessments comprised of audiological evaluations, cervical vestibular evoked myogenic potentials (cVEMPs, recognition of spoken phonemes in white noise (Rsp in wn, and auditory brainstem response to 500 Hz tone burst (ABR500 HZ. Twenty affected ears with decreased vestibular excitability as detected by abnormal cVEMPs revealed decreased scores of Rsp in wn and abnormal findings of ABR500 HZ. Both unaffected and normal ears had normal results. Multiple comparisons of mean values of cVEMPs and ABR500 HZ between three groups were significant (P<0.05, ANOVA. The correlation between RSP in wn and p13 latencies was significant. The peak-to-peak amplitudes showed significant correlation to RSP in wn. The correlation between RSP in wn and the latencies of n23 was significant. In high-level of noisy competing situations, healthy human saccular sensation can mediate the detection of low frequencies and possibly help in cochlear hearing for frequency and intensity discrimination. So, all human hearing is not cochlear.

  15. Cochlear implant: the family's perspective.

    Science.gov (United States)

    Vieira, Sheila de Souza; Dupas, Giselle; Chiari, Brasilia Maria

    2018-07-01

    To understand the family's experience of a child who uses a cochlear implant (CI). Specifically, to identify the difficulties, changes, and feelings entailed by deafness and the use of the CI; the coping strategies; and to understand the role of the family for the child with a CI. Qualitative research, using Symbolic Interactionism and Straussian Grounded Theory as the theoretical and methodological frameworks, respectively. Data collection instrument: semi-structured interview. A total of 9 families (32 individuals) participated in the study. The children's ages ranged from 6 to 11 years old (mean = 8.9 years old). Their experience is described in the following categories: Having to fight for results, Coping with difficult situations, Recognizing that you are not alone, Learning to overcome, and Having one's life restored by the implant. Cochlear implantation changes the direction of the child and the family's life by restoring the child's opportunity to hear and to obtain good results in her personal, social, and academic development. Even after implantation, the child continues to experience difficulties and requires the family's mobilization in order to be successful. The family is the principal actor in the process of the child's rehabilitation.

  16. Intraoperative Cochlear Implant Device Testing Utilizing an Automated Remote System: A Prospective Pilot Study.

    Science.gov (United States)

    Lohmann, Amanda R; Carlson, Matthew L; Sladen, Douglas P

    2018-03-01

    Intraoperative cochlear implant device testing provides valuable information regarding device integrity, electrode position, and may assist with determining initial stimulation settings. Manual intraoperative device testing during cochlear implantation requires the time and expertise of a trained audiologist. The purpose of the current study is to investigate the feasibility of using automated remote intraoperative cochlear implant reverse telemetry testing as an alternative to standard testing. Prospective pilot study evaluating intraoperative remote automated impedance and Automatic Neural Response Telemetry (AutoNRT) testing in 34 consecutive cochlear implant surgeries using the Intraoperative Remote Assistant (Cochlear Nucleus CR120). In all cases, remote intraoperative device testing was performed by trained operating room staff. A comparison was made to the "gold standard" of manual testing by an experienced cochlear implant audiologist. Electrode position and absence of tip fold-over was confirmed using plain film x-ray. Automated remote reverse telemetry testing was successfully completed in all patients. Intraoperative x-ray demonstrated normal electrode position without tip fold-over. Average impedance values were significantly higher using standard testing versus CR120 remote testing (standard mean 10.7 kΩ, SD 1.2 vs. CR120 mean 7.5 kΩ, SD 0.7, p automated testing with regard to the presence of open or short circuits along the array. There were, however, two cases in which standard testing identified an open circuit, when CR120 testing showed the circuit to be closed. Neural responses were successfully obtained in all patients using both systems. There was no difference in basal electrode responses (standard mean 195.0 μV, SD 14.10 vs. CR120 194.5 μV, SD 14.23; p = 0.7814); however, more favorable (lower μV amplitude) results were obtained with the remote automated system in the apical 10 electrodes (standard 185.4 μV, SD 11.69 vs. CR

  17. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    Science.gov (United States)

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-01-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences. Images Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 PMID:1452481

  18. Cytoarchitectonic and quantitative Golgi study of the hedgehog supraoptic nucleus.

    Science.gov (United States)

    Caminero, A A; Machín, C; Sanchez-Toscano, F

    1992-02-01

    A cytoarchitectural study was made of the supraoptic nucleus (SON) of the hedgehog with special attention to the quantitative comparison of its main neuronal types. The main purposes were (1) to relate the characteristics of this nucleus in the hedgehog (a primitive mammalian insectivorous brain) with those in the SONs of more evolutionarily advanced species; (2) to identify quantitatively the dendritic fields of the main neuronal types in the hedgehog SON and to study their synaptic connectivity. From a descriptive standpoint, 3 neuronal types were found with respect to the number of dendritic stems arising from the neuronal soma: bipolar neurons (48%), multipolar neurons (45.5%) and monopolar neurons (6.5%). Within the multipolar type 2 subtypes could be distinguished, taking into account the number of dendritic spines: (a) with few spines (93%) and (b) very spiny (7%). These results indicate that the hedgehog SON is similar to that in other species except for the very spiny neurons, the significance of which is discussed. In order to characterise the main types more satisfactorily (bipolar and multipolars with few spines) we undertook a quantitative Golgi study of their dendritic fields. Although the patterns of the dendritic field are similar in both neuronal types, the differences in the location of their connectivity can reflect functional changes and alterations in relation to the synaptic afferences.

  19. GABAergic projections to the oculomotor nucleus in the goldfish (Carassius auratus

    Directory of Open Access Journals (Sweden)

    M. Angeles eLuque

    2011-02-01

    Full Text Available The mammalian oculomotor nucleus receives a strong -aminobutyric acid (GABAergic synaptic input, whereas such projections have rarely been reported in fish. In order to determine whether this synaptic organization is preserved across vertebrates, we investigated the GABAergic projections to the oculomotor nucleus in the goldfish by combining retrograde transport of biotin dextran amine, injected into the antidromically identified oculomotor nucleus, and GABA immunohistochemistry. The main source of GABAergic afferents to the oculomotor nucleus was the ipsilateral anterior octaval nucleus, with only a few, if any, GABAergic neurons being located in the contralateral tangential and descending nuclei of the octaval column. In mammals there is a nearly exclusive ipsilateral projection from vestibular neurons to the oculomotor nucleus via GABAergic inhibitory inputs; thus, the vestibulooculomotor GABAergic circuitry follows a plan that appears to be shared throughout the vertebrate phylogeny. The second major source of GABAergic projections was the rhombencephalic reticular formation, primarily from the medial area but, to a lesser extent, from the inferior area. A few GABAergic oculomotor projecting neurons were also observed in the ipsilateral nucleus of the medial longitudinal fasciculus. The GABAergic projections from neurons located in both the reticular formation surrounding the abducens nucleus and the nucleus of the medial reticular formation have primarily been related to the control of saccadic eye movements. Finally, all retrogradely labeled internuclear neurons of the abducens nucleus, and neurons in the cerebellum (close to the caudal lobe, were negative for GABA. These data suggest that the vestibuloocular and saccadic inhibitory GABAergic systems appear early in vertebrate phylogeny to modulate the firing properties of the oculomotor nucleus motoneurons.

  20. Sensitivity to pulse phase duration in cochlear implant listeners: Effects of stimulation mode

    Science.gov (United States)

    Chatterjee, Monita; Kulkarni, Aditya M.

    2014-01-01

    The objective of this study was to investigate charge-integration at threshold by cochlear implant listeners using pulse train stimuli in different stimulation modes (monopolar, bipolar, tripolar). The results partially confirmed and extended the findings of previous studies conducted in animal models showing that charge-integration depends on the stimulation mode. The primary overall finding was that threshold vs pulse phase duration functions had steeper slopes in monopolar mode and shallower slopes in more spatially restricted modes. While the result was clear-cut in eight users of the Cochlear CorporationTM device, the findings with the six user of the Advanced BionicsTM device who participated were less consistent. It is likely that different stimulation modes excite different neuronal populations and/or sites of excitation on the same neuron (e.g., peripheral process vs central axon). These differences may influence not only charge integration but possibly also temporal dynamics at suprathreshold levels and with more speech-relevant stimuli. Given the present interest in focused stimulation modes, these results have implications for cochlear implant speech processor design and protocols used to map acoustic amplitude to electric stimulation parameters. PMID:25096116

  1. Cochlear implant: what the radiologist should know

    International Nuclear Information System (INIS)

    Gomes, Natalia Delage; Couto, Caroline Laurita Batista; Gaiotti, Juliana Oggioni; Costa, Ana Maria Doffemond; Ribeiro, Marcelo Almeida; Diniz, Renata Lopes Furletti Caldeira

    2013-01-01

    Cochlear implant is the method of choice in the treatment of deep sensorineural hypoacusis, particularly in patients where conventional amplification devices do not imply noticeable clinical improvement. Imaging findings are crucial in the indication or contraindication for such surgical procedure. In the assessment of the temporal bone, radiologists should be familiar with relative or absolute contraindication factors, as well as with factors that might significantly complicate the implantation. Some criteria such as cochlear nerve aplasia, labyrinthine and/or cochlear aplasia are still considered as absolute contraindications, in spite of studies bringing such criteria into question. Cochlear dysplasias constitute relative contraindications, among them labyrinthitis ossificans is highlighted. Other alterations may be mentioned as complicating agents in the temporal bone assessment, namely, hypoplasia of the mastoid process, aberrant facial nerve, otomastoiditis, otosclerosis, dehiscent jugular bulb, enlarged endolymphatic duct and sac. The experienced radiologist assumes an important role in the evaluation of this condition. (author)

  2. Cochlear implant: what the radiologist should know

    Directory of Open Access Journals (Sweden)

    Natalia Delage Gomes

    2013-06-01

    Full Text Available Cochlear implant is the method of choice in the treatment of deep sensorineural hypoacusis, particularly in patients where conventional amplification devices do not imply noticeable clinical improvement. Imaging findings are crucial in the indication or contraindication for such surgical procedure. In the assessment of the temporal bone, radiologists should be familiar with relative or absolute contraindication factors, as well as with factors that might significantly complicate the implantation. Some criteria such as cochlear nerve aplasia, labyrinthine and/or cochlear aplasia are still considered as absolute contraindications, in spite of studies bringing such criteria into question. Cochlear dysplasias constitute relative contraindications, among them labyrinthitis ossificans is highlighted. Other alterations may be mentioned as complicating agents in the temporal bone assessment, namely, hypoplasia of the mastoid process, aberrant facial nerve, otomastoiditis, otosclerosis, dehiscent jugular bulb, enlarged endolymphatic duct and sac. The experienced radiologist assumes an important role in the evaluation of this condition.

  3. Cochlear anatomy: CT and MR imaging

    International Nuclear Information System (INIS)

    Martinez, Manuel; Bruno, Claudio; Martin, Eduardo; Canale, Nancy; De Luca, Laura; Spina, Juan C. h

    2002-01-01

    The authors present a brief overview of the normal cochlear anatomy with CT and MR images in order to allow a more complete identification of the pathological findings in patients with perceptive hipoacusia. (author)

  4. Generation of induced neurons by direct reprogramming in the mammalian cochlea.

    Science.gov (United States)

    Nishimura, K; Weichert, R M; Liu, W; Davis, R L; Dabdoub, A

    2014-09-05

    Primary auditory neurons (ANs) in the mammalian cochlea play a critical role in hearing as they transmit auditory information in the form of electrical signals from mechanosensory cochlear hair cells in the inner ear to the brainstem. Their progressive degeneration is associated with disease conditions, excessive noise exposure and aging. Replacement of ANs, which lack the ability to regenerate spontaneously, would have a significant impact on research and advancement in cochlear implants in addition to the amelioration of hearing impairment. The aim of this study was to induce a neuronal phenotype in endogenous non-neural cells in the cochlea, which is the essential organ of hearing. Overexpression of a neurogenic basic helix-loop-helix transcription factor, Ascl1, in the cochlear non-sensory epithelial cells induced neurons at high efficiency at embryonic, postnatal and juvenile stages. Moreover, induced neurons showed typical properties of neuron morphology, gene expression and electrophysiology. Our data indicate that Ascl1 alone or Ascl1 and NeuroD1 is sufficient to reprogram cochlear non-sensory epithelial cells into functional neurons. Generation of neurons from non-neural cells in the cochlea is an important step for the regeneration of ANs in the mature mammalian cochlea. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. The arcuate nucleus of the C57BL/6J mouse hindbrain is a displaced part of the inferior olive.

    Science.gov (United States)

    Fu, Yu Hong; Watson, Charles

    2012-01-01

    The arcuate nucleus is a prominent cell group in the human hindbrain, characterized by its position on the pial surface of the pyramid. It is considered to be a precerebellar nucleus and has been implicated in the pathology of several disorders of respiration. An arcuate nucleus has not been convincingly demonstrated in other mammals, but we have found a similarly positioned nucleus in the C57BL/6J mouse. The mouse arcuate nucleus consists of a variable group of neurons lying on the pial surface of the pyramid. The nucleus is continuous with the ventrolateral part of the principal nucleus of the inferior olive and both groups are calbindin positive. At first we thought that this mouse nucleus was homologous with the human arcuate nucleus, but we have discovered that the neurons of the human nucleus are calbindin negative, and are therefore not olivary in nature. We have compared the mouse arcuate neurons with those of the inferior olive in terms of molecular markers and cerebellar projection. The neurons of the arcuate nucleus and of the inferior olive share three major characteristics: they both contain neurons utilizing glutamate, serotonin or acetylcholine as neurotransmitters; they both project to the contralateral cerebellum, and they both express a number of genes not present in the major mossy fiber issuing precerebellar nuclei. Most importantly, both cell groups express calbindin in an area of the ventral hindbrain almost completely devoid of calbindin-positive cells. We conclude that the neurons of the hindbrain mouse arcuate nucleus are a displaced part of the inferior olive, possibly separated by the caudal growth of the pyramidal tract during development. The arcuate nucleus reported in the C57BL/6J mouse can therefore be regarded as a subgroup of the rostral inferior olive, closely allied with the ventral tier of the principal nucleus. Copyright © 2012 S. Karger AG, Basel.

  6. [Cochlear implantation through the middle fossa approach].

    Science.gov (United States)

    Szyfter, W; Colletti, V; Pruszewicz, A; Kopeć, T; Szymiec, E; Kawczyński, M; Karlik, M

    2001-01-01

    The inner part of cochlear implant is inserted into inner ear during surgery through mastoid and middle ear. It is a classical method, used in the majority cochlear centers in the world. This is not a suitable method in case of chronic otitis media and middle ear malformation. In these cases Colletti proposed the middle fossa approach and cochlear implant insertion omitting middle ear structures. In patient with bilateral chronic otitis media underwent a few ears operations without obtaining dry postoperative cavity. Cochlear implantation through the middle fossa approach was performed in this patient. The bone fenster was cut, temporal lobe was bent and petrosus pyramid upper surface was exposed. When the superficial petrosal greater nerve, facial nerve and arcuate eminence were localised, the cochlear was open in the basal turn and electrode were inserted. The patient achieves good results in the postoperative speech rehabilitation. It confirmed Colletti tesis that deeper electrode insertion in the cochlear implantation through the middle fossa approach enable use of low and middle frequencies, which are very important in speech understanding.

  7. Optogenetic activation of serotonergic terminals facilitates GABAergic inhibitory input to orexin/hypocretin neurons

    OpenAIRE

    Chowdhury, Srikanta; Yamanaka, Akihiro

    2016-01-01

    Orexin/hypocretin neurons play a crucial role in the regulation of sleep/wakefulness, primarily in the maintenance of wakefulness. These neurons innervate wide areas of the brain and receive diverse synaptic inputs including those from serotonergic (5-HT) neurons in the raphe nucleus. Previously we showed that pharmacological application of 5-HT directly inhibited orexin neurons via 5-HT1A receptors. However, it was still unclear how 5-HT neurons regulated orexin neurons since 5-HT neurons co...

  8. Deconfinement of quarks and gluons in nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Gorenstein, M.I.

    2011-01-01

    The energy dependence of hadron production in relativistic nucleus-nucleus collisions reveals the anomalies. They were predicted as the signals of the deconfinement phase transition and observed by NA49 collaboration in Pb+Pb collisions at the CERN SPS. This indicates the onset of the deconfinement in central nucleus-nucleus collisions at about 30 AGeV.

  9. Diffractive ''semioptical'' model for nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Barashenkov, V.S.; Musulmanbekov, Zh.Zh.

    1979-01-01

    Diffraction Glauber theory for nucleus-nucleus collisions is considered in approximation when the initial nucleus interacts as a whole with nucleons of the target nucleus. Such an approach, being intermediate between precise Glauber theory and its optical limit, essentially simplifies numerical calculations and gives a good agreement with experiments as well. (author)

  10. Cortical Plasticity after Cochlear Implantation

    DEFF Research Database (Denmark)

    Petersen, Bjørn; Gjedde, Albert; Wallentin, Mikkel

    2013-01-01

    recently implanted adult implant recipients listened to running speech or speech-like noise in four sequential PET sessions at each milestone. CI listeners with postlingual hearing loss showed differential activation of left superior temporal gyrus during speech and speech-like stimuli, unlike CI listeners...... with prelingual hearing loss. Furthermore, Broca's area was activated as an effect of time, but only in CI listeners with postlingual hearing loss. The study demonstrates that adaptation to the cochlear implant is highly related to the history of hearing loss. Speech processing in patients whose hearing loss...... occurred after the acquisition of language involves brain areas associated with speech comprehension, which is not the case for patients whose hearing loss occurred before the acquisition of language. Finally, the findings confirm the key role of Broca's area in restoration of speech perception, but only...

  11. Music enjoyment with cochlear implantation.

    Science.gov (United States)

    Prevoteau, Charlotte; Chen, Stephanie Y; Lalwani, Anil K

    2018-10-01

    Since the advent of cochlear implant (CI) surgery in the 1960s, there have been remarkable technological and surgical advances enabling excellent speech perception in quiet with many CI users able to use the telephone. However, many CI users struggle with music perception, particularly with the pitch-based and melodic elements of music. Yet remarkably, despite poor music perception, many CI users enjoy listening to music based on self-report questionnaires, and prospective studies have suggested a disassociation between music perception and enjoyment. Music enjoyment is arguably a more functional measure of one's listening experience, and thus enhancing one's listening experience is a worthy goal. Recent studies have shown that re-engineering music to reduce its complexity may enhance enjoyment in CI users and also delineate differences in musical preferences from normal hearing listeners. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. The Human Cochlear Mechanical Nonlinearity Inferred via Psychometric Functions

    Directory of Open Access Journals (Sweden)

    Nizami Lance

    2013-12-01

    Extension of the model of Schairer and colleagues results in credible cochlear nonlinearities in man, suggesting that forward-masking provides a non-invasive way to infer the human mechanical cochlear nonlinearity.

  13. Continued expression of GATA3 is necessary for cochlear neurosensory development.

    Directory of Open Access Journals (Sweden)

    Jeremy S Duncan

    Full Text Available Hair cells of the developing mammalian inner ear are progressively defined through cell fate restriction. This process culminates in the expression of the bHLH transcription factor Atoh1, which is necessary for differentiation of hair cells, but not for their specification. Loss of several genes will disrupt ear morphogenesis or arrest of neurosensory epithelia development. We previously showed in null mutants that the loss of the transcription factor, Gata3, results specifically in the loss of all cochlear neurosensory development. Temporal expression of Gata3 is broad from the otic placode stage through the postnatal ear. It therefore remains unclear at which stage in development Gata3 exerts its effect. To better understand the stage specific effects of Gata3, we investigated the role of Gata3 in cochlear neurosensory specification and differentiation utilizing a LoxP targeted Gata3 line and two Cre lines. Foxg1(Cre∶Gata3(f/f mice show recombination of Gata3 around E8.5 but continue to develop a cochlear duct without differentiated hair cells and spiral ganglion neurons. qRT-PCR data show that Atoh1 was down-regulated but not absent in the duct whereas other hair cell specific genes such as Pou4f3 were completely absent. In addition, while Sox2 levels were lower in the Foxg1(Cre:Gata3(f/f cochlea, Eya1 levels remained normal. We conclude that Eya1 is unable to fully upregulate Atoh1 or Pou4f3, and drive differentiation of hair cells without Gata3. Pax2-Cre∶Gata3(f/f mice show a delayed recombination of Gata3 in the ear relative to Foxg1(Cre:Gata3(f/f . These mice exhibited a cochlear duct containing patches of partially differentiated hair cells and developed only few and incorrectly projecting spiral ganglion neurons. Our conditional deletion studies reveal a major role of Gata3 in the signaling of prosensory genes and in the differentiation of cochlear neurosenory cells. We suggest that Gata3 may act in combination with Eya1, Six1, and

  14. BDNF Increases Survival and Neuronal Differentiation of Human Neural Precursor Cells Cotransplanted with a Nanofiber Gel to the Auditory Nerve in a Rat Model of Neuronal Damage

    Directory of Open Access Journals (Sweden)

    Yu Jiao

    2014-01-01

    Full Text Available Objectives. To study possible nerve regeneration of a damaged auditory nerve by the use of stem cell transplantation. Methods. We transplanted HNPCs to the rat AN trunk by the internal auditory meatus (IAM. Furthermore, we studied if addition of BDNF affects survival and phenotypic differentiation of the grafted HNPCs. A bioactive nanofiber gel (PA gel, in selected groups mixed with BDNF, was applied close to the implanted cells. Before transplantation, all rats had been deafened by a round window niche application of β-bungarotoxin. This neurotoxin causes a selective toxic destruction of the AN while keeping the hair cells intact. Results. Overall, HNPCs survived well for up to six weeks in all groups. However, transplants receiving the BDNF-containing PA gel demonstrated significantly higher numbers of HNPCs and neuronal differentiation. At six weeks, a majority of the HNPCs had migrated into the brain stem and differentiated. Differentiated human cells as well as neurites were observed in the vicinity of the cochlear nucleus. Conclusion. Our results indicate that human neural precursor cells (HNPC integration with host tissue benefits from additional brain derived neurotrophic factor (BDNF treatment and that these cells appear to be good candidates for further regenerative studies on the auditory nerve (AN.

  15. Evolution of impedance field telemetry after one day of activation in cochlear implant recipients.

    Directory of Open Access Journals (Sweden)

    Hao-Chun Hu

    Full Text Available Changes in impedance between 24 hours and one month after cochlear implantation have never been explored due to the inability to switch on within one day. This study examined the effect of early activation (within 24 hours on the evolution of electrode impedance with the aim of providing information on the tissue-to-electrode interface when electrical stimulation was commenced one day post implantation.We performed a retrospective review at a single institution. Patients who received a Nucleus 24RECA implant system (Cochlear, Sydney, Australia and underwent initial switch-on within 24 hours postoperatively were included. Impedance measurements were obtained intraoperatively and postoperatively at 1 day, 1 week, 4 weeks, and 8 weeks.A significant drop in impedance was noted 1 day after an initial activation within 24 hours followed by a significant rise in impedance in all channels until 1 week, after which the impedance behaved differently in different segments. Basal and mid-portion electrodes revealed a slight increase while apical electrodes showed a slight decrease in impedance from 1 week to 8 weeks postoperatively. Impedance was relatively stable 4 weeks after surgery.This is the first study to report the evolution of impedance in all channels between initial mapping 1 day and 1 month after cochlear implantation. The underlying mechanism for the differences in behavior between different segments of the electrode may be associated with the combined effect of dynamics among the interplay of cell cover formation, electrical stimulation, and fibrotic reaction.

  16. Revision surgery due to magnet dislocation in cochlear implant patients: an emerging complication.

    Science.gov (United States)

    Hassepass, Frederike; Stabenau, Vanessa; Maier, Wolfgang; Arndt, Susan; Laszig, Roland; Beck, Rainer; Aschendorff, Antje

    2014-01-01

    To analyze the cause and effect of magnet dislocation in cochlear implant (CI) recipients requiring magnet revision surgery for treatment. Retrospective study. Tertiary referral center. Case reports from 1,706 CI recipients consecutively implanted from January 2000 to December 2011 were reviewed. The number of cases requiring magnet revision surgery was assessed. Revision surgery involving magnet removal or replacement was indicated in 1.23% (21/1,706), of all CI recipients. Magnet dislocation occurring during magnetic resonance tomography (MRI), at 1.5 Tesla (T), with the magnet in place and with the application of compression bandaging around the head, was the main cause for revision surgery in 47.62% (10/21) of the affected cases. All 10 cases were implanted with Cochlear Nucleus cochlear implants. These events occurred, despite adherence to current recommendations of the manufacturer. The present study underlines that MRI examination is the main cause of magnet dislocation. The use of compressive bandaging when using 1.5-T MRI does not eliminate the risk of magnet dislocation. Additional cautionary measures are for required for conditional MRI. We recommend X-ray examination after MRI to determine magnet dislocation and avoid major complications in all cases reporting pain during or after MRI. Additional research regarding silicon magnet pocket design for added retention is needed. Effective communication of guidelines for precautionary measures during MRI examination in CI patients is mandatory for all clinicians involved. MRI in CI recipients should be indicated with caution.

  17. Dissipation in nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Santanu Pal

    1984-01-01

    This paper deals with the mechanism of one- and two-body dissipations in nucleus-nucleus collisions. The average energy transferred to nuclear excitations is calculated using a time-dependent density matrix approach with lowest-order approximations. Considering the nuclei as Fermi gases, and using a gaussian-type NN interaction as the basic perturbation, simplified expressions are obtained for energy dissipations. These expressions are quite instructive to follow a number of interesting aspects of one- and two-body dissipations. It is theoretically observed that the memory time for the two-body dissipation is significantly smaller than that of one-body dissipation. A threshold-type dependence of the transferred energy on the relative velocity between the two nuclei is also observed. This threshold velocity is found to be related with the intrinsic nucleon kinetic energy for two-body dissipation and with the nuclear size for the one-body case. This observation further suggests that the total dissipated energy is shared between the two nuclei approximately in the ratio of their masses. The physical origin of these observations is also explained. Numerical calculations further illustrate some characteristic features of one- and two-body dissipations. (orig.)

  18. High energy nucleus-nucleus scattering and matter radius of unstable nucleus

    International Nuclear Information System (INIS)

    Sato, H.; Okuhara, Y.

    1985-07-01

    The interaction cross sections of high energy nucleus-nucleus scattering have been studied with the Glauber Model and Hartree-Fock like variational calculation for the nuclear structure. It is found that the experimental interaction cross sections of the light unstable nucleus-stable nucleus scatterings measured by INS-LBL collaboration are well reproduceable. (author)

  19. A stereological study of the mediodorsal thalamic nucleus in Down syndrome

    DEFF Research Database (Denmark)

    Karlsen, A S; Korbo, S; Uylings, H B M

    2014-01-01

    The total number of neurons and glial cells in the mediodorsal thalamic (MDT) nucleus of four aged females with Down syndrome (DS; mean age 69years) was estimated and compared to six age- and sex-matched controls. The MDT nucleus was delineated on coronal sections, and cell numbers (large and small...

  20. Neurochemistry of olivocochlear neurons in the hamster.

    Science.gov (United States)

    Reuss, Stefan; Disque-Kaiser, Ursula; Antoniou-Lipfert, Patricia; Gholi, Maryam Najaf; Riemann, Elke; Riemann, Randolf

    2009-04-01

    The present study was conducted to characterize the superior olivary complex (SOC) of the lower brain stem in the pigmented Djungarian hamster Phodopus sungorus. Using Nissl-stained serial cryostat sections from fresh-frozen brains, we determined the borders of the SOC nuclei. We also identified olivocochlear (OC) neurons by retrograde neuronal tracing upon injection of Fluoro-Gold into the scala tympani. To evaluate the SOC as a putative source of neuronal nitric oxide synthase (nNOS), arginine-vasopressin (AVP), oxytocin (OT), vasoactive intestinal polypeptide (VIP), or pituitary adenylate cyclase-activating polypeptide (PACAP) that were all found in the cochlea, we conducted immunohistochemistry on sections exhibiting retrogradely labeled neurons. We did not observe AVP-, OT-, or VIP-immunoreactivity, neither in OC neurons nor in the SOC at all, revealing that cochlear AVP, OT, and VIP are of nonolivary origin. However, we found nNOS, the enzyme responsible for nitric oxide synthesis in neurons, and PACAP in neuronal perikarya of the SOC. Retrogradely labeled neurons of the lateral olivocochlear (LOC) system in the lateral superior olive did not contain PACAP and were only infrequently nNOS-immunoreactive. In contrast, some shell neurons and some of the medial OC (MOC) system exhibited immunofluorescence for either substance. Our data obtained from the dwarf hamster Phodopus sungorus confirm previous observations that a part of the LOC system is nitrergic. They further demonstrate that the medial olivocochlear system is partly nitrergic and use PACAP as neurotransmitter or modulator.

  1. Particle correlations in proton-nucleus and nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Nagamiya, Sh.

    1981-01-01

    Particle correlations in proton-nucleus and nucleus-nucleus collisions at energies of 1-2 GeV/nucleon are investigated. The problems of measurement of the mean free path lambda of protons inside the nucleus and the interaction radius of nucleus-nucleus collisions is considered. The value of lambda has been determined in two-proton coincidence experiment in proton-nucleus interaction at 800 MeV. The observed value of lambda is slightly longer than the expected from free nucleon-nucleon collisions. Some preliminary results on proton emission beyond free nucleon-nucleon kinemaics are given

  2. Some experimental results of the investigation of hadron-nucleus and nucleus-nucleus interactions

    International Nuclear Information System (INIS)

    Azimov, S.A.; Gulamov, K.G.; Chernov, G.M.

    1978-01-01

    Recent experimental data on the hadron-nucleus and nucleus-nucleus inelastic interactions are analyzed. A particular attention is paid to the description of the leading hadron spectra and of the spectra of nucleon recoils in hadron-nucleus interactions. Some of the results of the experimental studies of correlations between secondary particles are discussed. This discussion demonstrates that an analysis of the multiparticle phenomena is very promising regarding the discrimination between the different models for the hadron-nucleus and nucleus-nucleus interactions. It is pointed out that the actual mechanism of the hadron-nucleus and nucleus-nucleus interactions is a rather complex one and can be described comprehensively by none of the existing models

  3. Retrolabyrinthine approach for cochlear nerve preservation in neurofibromatosis type 2 and simultaneous cochlear implantation

    Directory of Open Access Journals (Sweden)

    Bento, Ricardo Ferreira

    2014-01-01

    Full Text Available Introduction: Few cases of cochlear implantation (CI in neurofibromatosis type 2 (NF2 patients had been reported in the literature. The approaches described were translabyrinthine, retrosigmoid or middle cranial fossa. Objectives: To describe a case of a NF2- deafened-patient who underwent to vestibular schwannoma resection via RLA with cochlear nerve preservation and CI through the round window, at the same surgical time. Resumed Report: A 36-year-old woman with severe bilateral hearing loss due to NF2 was submitted to vestibular schwannoma resection and simultaneous CI. Functional assessment of cochlear nerve was performed by electrical promontory stimulation. Complete tumor removal was accomplishment via RLA with anatomic and functional cochlear and facial nerve preservation. Cochlear electrode array was partially inserted via round window. Sound field hearing threshold improvement was achieved. Mean tonal threshold was 46.2 dB HL. The patient could only detect environmental sounds and human voice but cannot discriminate vowels, words nor do sentences at 2 years of follow-up. Conclusion: Cochlear implantation is a feasible auditory restoration option in NF2 when cochlear anatomic and functional nerve preservation is achieved. The RLA is adequate for this purpose and features as an option for hearing preservation in NF2 patients.

  4. Nonlinear development of the populations of neurons expressing c-Fos under sustained electrical intracochlear stimulation in the rat auditory brainstem.

    Science.gov (United States)

    Rosskothen-Kuhl, Nicole; Illing, Robert-Benjamin

    2010-08-06

    The immediate-early-gene c-fos is among the first genes to be expressed following sensory-invoked neuronal activity. Its gene product c-Fos forms the limiting monomer of the heterodimeric activator protein-1 transcription factor that triggers various genes involved in neuroplastic remodeling. This study investigated the pattern of c-Fos expression in anteroventral (AVCN) and dorsal cochlear nucleus (DCN) and central inferior colliculus (CIC) after 45 min, 73 min, 2 h, 3:15 h and 5 h of unilateral electrical intracochlear stimulation (EIS) at 50 Hz in anaesthetized rats. Following EIS, tonotopic c-Fos expression was observed for each stimulation time in ipsilateral AVCN, DCN bilaterally, and contralateral CIC. By counting c-Fos positive nuclei, we discovered temporal non-linearities in the size of the respective population of c-Fos expressing neurons. In all regions investigated, the populations significantly increased from 73 min to 2 h but decreased towards 3:15 h. In AVCN, the number rose again by 5 h of EIS. Remarkably, the same was noted for neurons with large nuclei in deep DCN. In both regions, the population of responsive neurons shifted spatially: In central AVCN, the density of c-Fos positive cells increased significantly from 2 to 5h with medial and lateral regions remaining unchanged. In DCN, the density of large c-Fos positive nuclei fell in the upper and rose in the deep layers from 45 min to 5h of EIS. In conclusion, spatiotemporally varying recruitments of neuronal subpopulations into cellular networks responding to specific patterns of sensory activity take place in the auditory brainstem. Copyright 2010 Elsevier B.V. All rights reserved.

  5. The role of gamma-aminobutyric acid/glycinergic synaptic transmission in mediating bilirubin-induced hyperexcitation in developing auditory neurons.

    Science.gov (United States)

    Yin, Xin-Lu; Liang, Min; Shi, Hai-Bo; Wang, Lu-Yang; Li, Chun-Yan; Yin, Shan-Kai

    2016-01-05

    Hyperbilirubinemia is a common clinical phenomenon observed in human newborns. A high level of bilirubin can result in severe jaundice and bilirubin encephalopathy. However, the cellular mechanisms underlying bilirubin excitotoxicity are unclear. Our previous studies showed the action of gamma-aminobutyric acid (GABA)/glycine switches from excitatory to inhibitory during development in the ventral cochlear nucleus (VCN), one of the most sensitive auditory nuclei to bilirubin toxicity. In the present study, we investigated the roles of GABAA/glycine receptors in the induction of bilirubin hyperexcitation in early developing neurons. Using the patch clamp technique, GABAA/glycine receptor-mediated spontaneous inhibitory synaptic currents (sIPSCs) were recorded from bushy and stellate cells in acute brainstem slices from young mice (postnatal day 2-6). Bilirubin significantly increased the frequency of sIPSCs, and this effect was prevented by pretreatments of slices with either fast or slow Ca(2+) chelators BAPTA-AM and EGTA-AM suggesting that bilirubin can increase the release of GABA/glycine via Ca(2+)-dependent mechanisms. Using cell-attached recording configuration, we found that antagonists of GABAA and glycine receptors strongly attenuated spontaneous spiking firings in P2-6 neurons but produced opposite effect in P15-19 neurons. Furthermore, these antagonists reversed bilirubin-evoked hyperexcitability in P2-6 neurons, indicating that excitatory action of GABA/glycinergic transmission specifically contribute to bilirubin-induced hyperexcitability in the early stage of development. Our results suggest that bilirubin-induced enhancement of presynaptic release GABA/Glycine via Ca(2+)-dependent mechanisms may play a critical role in mediating neuronal hyperexcitation associated with jaundice, implicating potential new strategies for predicting, preventing, and treating bilirubin neurotoxicity. Copyright © 2015. Published by Elsevier Ireland Ltd.

  6. Usher syndrome and cochlear implantation.

    Science.gov (United States)

    Loundon, Natalie; Marlin, Sandrine; Busquet, Denise; Denoyelle, Françoise; Roger, Gilles; Renaud, Francis; Garabedian, Erea Noel

    2003-03-01

    To evaluate the symptoms leading to diagnosis and the quality of rehabilitation after cochlear implantation in Usher syndrome. Retrospective cohort study. ENT department of a tertiary referral hospital. Among 210 patients given an implantation in the Ear, Nose, and Throat department, 185 were congenitally deaf and 13 had Usher syndrome (7.0%). Five had a family history of Usher, and eight were sporadic cases. Eleven cases were Usher type I, one was Usher type III, and one was not classified. The age at implantation ranged from 18 months to 44 years (mean, 6 years 1 month). The mean follow-up was 52 months (range, 9 months to 9 years). All patients had audiophonological and clinical examination, computed tomography scan of the temporal bones, ophthalmologic examination with fundoscopy, and an electroretinogram. Cerebral magnetic resonance imaging and vestibular examination were performed in 9 of 13 and 10 of 13 cases, respectively. Logopedic outcome measured preimplant and postimplant closed- and open-set word recognition and oral expression at follow-up. The most frequent initial sign of Usher syndrome was delayed walking, with a mean age of 20 months. Among the 172 other congenitally deaf children with implants, when deafness was not associated with other neurologic disorders, the mean age at walking was 14 months (p < 0.001). The fundoscopy was always abnormal after the age of 5 years, and the electroretinogram was abnormal in all cases. Vestibular function was abnormal in all but one case (nonclassified). The computed tomography scan and the magnetic resonance imaging were always normal. Logopedic results with cochlear implants showed good perception skills in all but one case. The best perceptive results were obtained in children implanted before the age of 9 years. Oral language had significantly progressed in 9 of 13 at follow-up. There was no relation between the visual acuity and the logopedic results. The earliest clinical sign associated with deafness

  7. Parental expectations and outcomes of pediatric cochlear implantation.

    Science.gov (United States)

    Piazza, Elizabeth; Kandathil, Cherian; Carron, Jeffrey D

    2009-10-01

    Cochlear implants have been used with increasing frequency over the past twenty years, including very young patients. To determine if parents are satisfied with their children's performance after cochlear implantation. Survey mailed to parents of children receiving cochlear implants. 31 questionnaires were returned out of 69 mailed (45 %). The vast majority of responding parents felt that their children benefited substantially from cochlear implant surgery. Cochlear implantation is effective in helping children develop auditory-oral communication skills. Access to auditory/oral communication programs in this state remains an obstacle in postoperative habilitation.

  8. Multifragmentation in peripheral nucleus-nucleus collisions

    International Nuclear Information System (INIS)

    Trautmann, W.; Adloff, J.C.; Bouissou, P.; Hubele, J.; Imme, G.; Iori, I.; Kreutz, P.; Leray, S.; Lindenstruth, V.; Liu, Z.; Lynen, U.; Meijer, R.J.; Milkau, U.; Moroni, A.; Mueller, W.F.J.; Ngo, C.; Ogilvie, C.A.; Pochodzalla, J.; Raciti, G.; Rudolf, G.; Schuettauf, A.; Stuttge, L.

    1993-10-01

    The complete fragmentation of highly excited nuclear systems into fragments of intermediate mass is observed in heavy-ion reactions at relativistic bombarding energies in the range of several hundreds of MeV per nucleon. Similar features are found for peripheral collisions between heavy nuclei and for more central collisions between a heavy and a light nucleus. The partition space explored in multifragment decays is well described by the statistical multifragmentation models. The expansion before breakup is confirmed by the analysis of the measured fragment energies of ternary events in their own rest frame. Collective radial flow is confined to rather small values in these peripheral-type reactions. Many conceptually different models seem to be capable of reproducing the charge correlations measured for the multifragment decays. (orig.)

  9. Evaluation of a wireless audio streaming accessory to improve mobile telephone performance of cochlear implant users.

    Science.gov (United States)

    Wolfe, Jace; Morais Duke, Mila; Schafer, Erin; Cire, George; Menapace, Christine; O'Neill, Lori

    2016-01-01

    The objective of this study was to evaluate the potential improvement in word recognition in quiet and in noise obtained with use of a Bluetooth-compatible wireless hearing assistance technology (HAT) relative to the acoustic mobile telephone condition (e.g. the mobile telephone receiver held to the microphone of the sound processor). A two-way repeated measures design was used to evaluate differences in telephone word recognition obtained in quiet and in competing noise in the acoustic mobile telephone condition compared to performance obtained with use of the CI sound processor and a telephone HAT. Sixteen adult users of Nucleus cochlear implants and the Nucleus 6 sound processor were included in this study. Word recognition over the mobile telephone in quiet and in noise was significantly better with use of the wireless HAT compared to performance in the acoustic mobile telephone condition. Word recognition over the mobile telephone was better in quiet when compared to performance in noise. The results of this study indicate that use of a wireless HAT improves word recognition over the mobile telephone in quiet and in noise relative to performance in the acoustic mobile telephone condition for a group of adult cochlear implant recipients.

  10. Nicotinic activation of laterodorsal tegmental neurons

    DEFF Research Database (Denmark)

    Ishibashi, Masaru; Leonard, Christopher S; Kohlmeier, Kristi A

    2009-01-01

    Identifying the neurological mechanisms underlying nicotine reinforcement is a healthcare imperative, if society is to effectively combat tobacco addiction. The majority of studies of the neurobiology of addiction have focused on dopamine (DA)-containing neurons of the ventral tegmental area (VTA......). However, recent data suggest that neurons of the laterodorsal tegmental (LDT) nucleus, which sends cholinergic, GABAergic, and glutamatergic-containing projections to DA-containing neurons of the VTA, are critical to gating normal functioning of this nucleus. The actions of nicotine on LDT neurons...... are unknown. We addressed this issue by examining the effects of nicotine on identified cholinergic and non-cholinergic LDT neurons using whole-cell patch clamp and Ca(2+)-imaging methods in brain slices from mice (P12-P45). Nicotine applied by puffer pipette or bath superfusion elicited membrane...

  11. Antiproton-nucleus interaction

    International Nuclear Information System (INIS)

    Gibbs, W.R.

    1984-01-01

    Several facets of antinucleon-nucleus interactions are explored. The topics treated are: coherent interactions, production of unusual states and particles in the nuclear medium, and the creation of extreme states of matter by antimatter annihilation. It is found that temperatures of the magnitude necessary to achieve the predicted quark-gluon phase transition are obtained. 20 references

  12. Nucleus accumbens and impulsivity

    NARCIS (Netherlands)

    Basar, K.; Sesia, T.; Groenewegen, H.J.; Steinbusch, H.W.; Visser-vandewalle, V.; Temel, Y.

    2010-01-01

    The multifaceted concept of impulsivity implies that different impulsivity aspects, mediated by different neural processes, influence behavior at different levels. The nucleus accumbens (NAc) is a key component of the neural processes regulating impulsivity. In this review, we discuss the findings

  13. Quasi-elastic shadowing in nucleus-nucleus elastic scattering

    Energy Technology Data Exchange (ETDEWEB)

    Dymarz, R; Malecki, A [Institute of Nuclear Physics, Krakow (Poland); Gluski, K [Institute of Nuclear Research, Warsaw (Poland); Picchi, P [Turin Univ. (Italy). Ist. di Fisica; Consiglio Nazionale delle Ricerche, Turin (Italy). Lab. di Cosmo-Geofisica)

    1979-01-06

    The complete evaluation of the Glauber multiple-scattering series for nucleus-nucleus collisions is a very difficult task and that is why various approximate formulae were proposed. In this work some of these approximations are discussed.

  14. Cochlear implant after bacterial meningitis.

    Science.gov (United States)

    Bille, Jesper; Ovesen, Therese

    2014-06-01

    The aim of this retrospective case study at a tertiary referral center was to investigate the outcome of cochlear implantation (CI) in children with sensorineural hearing loss due to meningitis compared to CI in children with deafness due to other reasons. This post-meningial group (PMG) consisted of 22 children undergoing CI due to deafness induced by meningitis, between December 1996 and January 2012. Five children had bilateral simultaneous implantation. None was excluded and the children were followed for at least 3 years. Operations were carried out by one of two surgeons using similar techniques in all cases. Each patient from the PMG was matched 2:1 with children having implantation for other reasons according to age and follow up (control group). Overall, the median category of auditory performance (CAP) and speech intelligibility rating (SIR) score were not statistically significantly different between the two groups. The presence of additional central nervous system (CNS) disorders (post-meningeal sequelae), however, correlated significantly with poorer outcome CI was a safe procedure without surgical complications in the present study. It is possible to restore auditory capacity and speech performance to a degree comparable to children undergoing implantation for other reasons. A statistically important variable is secondary CNS involvement. The rehabilitation program after CI should be adjusted according to these additional handicaps. It is recommended to screen meningitis patients as fast as possible to identify those with hearing loss and initiate treatment with hearing aids or CI. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  15. Fluctuating Estrogen and Progesterone Receptor Expression in Brainstem Norepinephrine Neurons through the Rat Estrous Cycle

    NARCIS (Netherlands)

    Haywood, S.A.; Simonian, S.X.; Beek, van der E.M.; Bicknell, R.J.; Herbison, A.E.

    1999-01-01

    Norepinephrine (NE) neurons within the nucleus tractus solitarii (NTS; A2 neurons) and ventrolateral medulla (A1 neurons) represent gonadal steroid-dependent components of several neural networks regulating reproduction. Previous studies have shown that both A1 and A2 neurons express estrogen

  16. Tinnitus and Sleep Difficulties After Cochlear Implantation.

    Science.gov (United States)

    Pierzycki, Robert H; Edmondson-Jones, Mark; Dawes, Piers; Munro, Kevin J; Moore, David R; Kitterick, Pádraig T

    To estimate and compare the prevalence of and associations between tinnitus and sleep difficulties in a sample of UK adult cochlear implant users and those identified as potential candidates for cochlear implantation. The study was conducted using the UK Biobank resource, a population-based cohort of 40- to 69-year olds. Self-report data on hearing, tinnitus, sleep difficulties, and demographic variables were collected from cochlear implant users (n = 194) and individuals identified as potential candidates for cochlear implantation (n = 211). These "candidates" were selected based on (i) impaired hearing sensitivity, inferred from self-reported hearing aid use and (ii) impaired hearing function, inferred from an inability to report words accurately at negative signal to noise ratios on an unaided closed-set test of speech perception. Data on tinnitus (presence, persistence, and related distress) and on sleep difficulties were analyzed using logistic regression models controlling for gender, age, deprivation, and neuroticism. The prevalence of tinnitus was similar among implant users (50%) and candidates (52%; p = 0.39). However, implant users were less likely to report that their tinnitus was distressing at its worst (41%) compared with candidates (63%; p = 0.02). The logistic regression model suggested that this difference between the two groups could be explained by the fact that tinnitus was less persistent in implant users (46%) compared with candidates (72%; p reported difficulties with sleep were similar among implant users (75%) and candidates (82%; p = 0.28), but participants with tinnitus were more likely to report sleep difficulties than those without (p explanation is supported by the similar prevalence of sleep problems among implant users and potential candidates for cochlear implantation, despite differences between the groups in tinnitus persistence and related emotional distress. Cochlear implantation may therefore not be an appropriate intervention

  17. Mechanisms of High Energy Hadron-Nucleus and Nucleus-Nucleus Collision Processes

    International Nuclear Information System (INIS)

    Strugalski, Z.

    1994-01-01

    Mechanisms of high energy hadron-nucleus and nucleus-nucleus collision processes are depicted qualitatively, as prompted experimentally. In hadron-nucleus collisions the interaction of the incident hadron in intranuclear matter is localized in small cylindrical volume, with the radius as large as the strong interaction range is, centered on the hadron course in the nucleus. The nucleon emission is induced by the hadron in its passing through the nucleus; particles are produced via intermediate objects produced in 2 → 2 endoergic reactions of the hadron and its successors with downstream nucleons. In nucleus-nucleus collisions, the outcome of the reaction appears as the composition of statistically independent hadron-nucleus collision outcomes at various impact parameters. Observable effects supporting such mechanisms are discussed. 51 refs

  18. Afferent projections to the deep mesencephalic nucleus in the rat

    International Nuclear Information System (INIS)

    Veazey, R.B.; Severin, C.M.

    1982-01-01

    Afferent projections to the deep mesencephalic nucleus (DMN) of the rat were demonstrated with axonal transport techniques. Potential sources for projections to the DMN were first identified by injecting the nucleus with HRP and examining the cervical spinal cord, brain stem, and cortex for retrogradely labeled neurons. Areas consistently labeled were then injected with a tritiated radioisotope, the tissue processed for autoradiography, and the DMN examined for anterograde labeling. Afferent projections to the medial and/or lateral parts of the DMN were found to originate from a number of spinal, bulbar, and cortical centers. Rostral brain centers projecting to both medial and lateral parts of the DMN include the ipsilateral motor and somatosensory cortex, the entopeduncular nucleus, and zona incerta. at the level of the midbrain, the ipsilateral substantia nigra and contralateral DMN likewise project to the DMN. Furthermore, the ipsilateral superior colliculus projects to the DMN, involving mainly the lateral part of the nucleus. Afferents from caudal centers include bilateral projections from the sensory nucleus of the trigeminal complex and the nucleus medulla oblongata centralis, as well as from the contralateral dentate nucleus. The projections from the trigeminal complex and nucleus medullae oblongatae centralis terminate in the intermediate and medial parts of the DMN, whereas projections from the contralateral dentate nucleus terminate mainly in its lateral part. In general, the afferent connections of the DMN arise from diverse areas of the brain. Although most of these projections distribute throughout the entire extent of the DMN, some of them project mainly to either medial or lateral parts of the nucleus, thus suggesting that the organization of the DMN is comparable, at least in part, to that of the reticular formation of the pons and medulla, a region in which hodological differences between medial and lateral subdivisions are known to exist

  19. Music Therapy for Preschool Cochlear Implant Recipients

    Science.gov (United States)

    Gfeller, Kate; Driscoll, Virginia; Kenworthy, Maura; Van Voorst, Tanya

    2010-01-01

    This paper provides research and clinical information relevant to music therapy for preschool children who use cochlear implants (CI). It consolidates information from various disciplinary sources regarding (a) cochlear implantation of young prelingually-deaf children (~age 2-5), (b) patterns of auditory and speech-language development, and (c) research regarding music perception of children with CIs. This information serves as a foundation for the final portion of the article, which describes typical music therapy goals and examples of interventions suitable for preschool children. PMID:23904691

  20. Hindbrain Catecholamine Neurons Activate Orexin Neurons During Systemic Glucoprivation in Male Rats.

    Science.gov (United States)

    Li, Ai-Jun; Wang, Qing; Elsarelli, Megan M; Brown, R Lane; Ritter, Sue

    2015-08-01

    Hindbrain catecholamine neurons are required for elicitation of feeding responses to glucose deficit, but the forebrain circuitry required for these responses is incompletely understood. Here we examined interactions of catecholamine and orexin neurons in eliciting glucoprivic feeding. Orexin neurons, located in the perifornical lateral hypothalamus (PeFLH), are heavily innervated by hindbrain catecholamine neurons, stimulate food intake, and increase arousal and behavioral activation. Orexin neurons may therefore contribute importantly to appetitive responses, such as food seeking, during glucoprivation. Retrograde tracing results showed that nearly all innervation of the PeFLH from the hindbrain originated from catecholamine neurons and some raphe nuclei. Results also suggested that many catecholamine neurons project collaterally to the PeFLH and paraventricular hypothalamic nucleus. Systemic administration of the antiglycolytic agent, 2-deoxy-D-glucose, increased food intake and c-Fos expression in orexin neurons. Both responses were eliminated by a lesion of catecholamine neurons innervating orexin neurons using the retrogradely transported immunotoxin, anti-dopamine-β-hydroxylase saporin, which is specifically internalized by dopamine-β-hydroxylase-expressing catecholamine neurons. Using designer receptors exclusively activated by designer drugs in transgenic rats expressing Cre recombinase under the control of tyrosine hydroxylase promoter, catecholamine neurons in cell groups A1 and C1 of the ventrolateral medulla were activated selectively by peripheral injection of clozapine-N-oxide. Clozapine-N-oxide injection increased food intake and c-Fos expression in PeFLH orexin neurons as well as in paraventricular hypothalamic nucleus neurons. In summary, catecholamine neurons are required for the activation of orexin neurons during glucoprivation. Activation of orexin neurons may contribute to appetitive responses required for glucoprivic feeding.

  1. Follow-up of cochlear implant use in patients who developed bacterial meningitis following cochlear implantation.

    Science.gov (United States)

    Mancini, Patrizia; D'Elia, Chiara; Bosco, Ersilia; De Seta, Elio; Panebianco, Valeria; Vergari, Valeria; Filipo, Roberto

    2008-08-01

    The present study is a long-term follow-up of speech perception outcomes and cochlear implant use in three cases of meningitis that occurred after cochlear implantation. Case series study. Study was performed on three children implanted with different models of Clarion devices, two of them with positioner. Recognition and comprehension were assessed via the Italian adaptation of GASP (TAP) test, and phonetically balanced bi-syllabic words in open-set. High resolution computed tomography scan acquisition was performed to obtain axial coronal and oblique multiplanar reconstructions of the cochlea. Two patients were affected by enlarged cochlear acqueduct and Mondini malformation the first carrying positioner. One patient had a normal cochlea, and the positioner could have been the main cause of bacterial spread. As a consequence of meningitis the child with normal cochlea and the other with enlarged vestibular acqueduct developed cochlear ossification, increased M-level and worsening of hearing outcomes. The child with Mondini malformation developed facial nerve stimulation. Contralateral implantation was performed in the first two patients. Bacterial meningitis occurring after cochlear implantation may induce cochlear ossification, facial nerve stimulation, and permanent or temporary loss of implant use. Planned follow-up with high resolution computed tomography and evaluation of M-levels could be useful prognostic tools in the management of these patients.

  2. Study of Relativistic Nucleus - Nucleus Collisions

    CERN Multimedia

    2002-01-01

    The aim of the experiment is to survey the reaction mechanisms involved in the collision of 60~GeV/nucleon and 200~GeV/nucleon light ions ($^{16}$0 and $^{32}$S provided by a new GSI-LBL injector) with different nuclei, to determine the stopping power of nuclear matter and to search for evidence of the formation of quark matter by comparison to hadron-nucleus reactions at the same incident energies. \\\\ The experimental set-up consists of a 2 m Streamer Chamber in the Vertex Magnet used to detect all the charged particles emerging from the interaction as well as the neutral strange particles that decay inside the chamber. The high energy of the forward-going particles are detected by four sets of calorimeters. A highly segmented Photon Position Detector (PPD) backed up by a 240 segment Ring Calorimeter will cover one unit of rapidity around mid-rapidity. An Intermediate Calorimeter will cover the rest of the forward phase space except for the region around beam rapidity, where a Veto Calorimeter will detect be...

  3. Tyrosine Hydroxylase (TH)- and Aromatic-L-Amino Acid Decarboxylase (AADC)-Immunoreactive Neurons of the Common Marmoset (Callithrix jacchus) Brain: An Immunohistochemical Analysis

    Science.gov (United States)

    Karasawa, Nobuyuki; Hayashi, Motoharu; Yamada, Keiki; Nagatsu, Ikuko; Iwasa, Mineo; Takeuchi, Terumi; Uematsu, Mitsutoshi; Watanabe, Kazuko; Onozuka, Minoru

    2007-01-01

    From the perspective of comparative morphology, the distribution of non-monoaminergic neurons in the common marmoset (Callithrix jacchus) was investigated using an immunohistochemical method with specific antibodies to tyrosine hydroxylase (TH) and aromatic-L-amino acid decarboxylase (AADC). TH-immunoreactive (IR) neurons (but not AADC-IR) neurons were observed in the olfactory tubercle, preoptic suprachiasmatic nucleus, periventricular hypothalamic nucleus, arcuate nucleus, paraventricular nucleus, periaqueductal gray matter, medial longitudinal fasciculus, substantia nigra, and nucleus solitaris. In contrast, AADC-IR (but not TH-IR), small, oval and spindle-shaped neurons were sparsely distributed in the following areas: the hypothalamus from the anterior nucleus to the lateral nucleus, the dorsomedial nucleus, the dorsomedial area of the medial mammillary nucleus and the arcuate nucleus; the midbrain, including the stria medullaris and substantia nigra; and the medulla oblongata, including the dorsal area of the nucleus solitaris and the medullary reticular nucleus. The distribution of AADC-IR neurons was not as extensive in the marmoset as it is in rats. However, these neurons were located in the marmoset, but not the rat substantia nigra. Furthermore, AADC-IR neurons that are present in the human striatum were absent in that of the marmoset. The present results indicate that the distribution of non-monoaminergic neurons in the brain of the common marmoset is unique and different from that in humans and rodents. PMID:17653300

  4. Impedance and electrically evoked compound action potential (ECAP drop within 24 hours after cochlear implantation.

    Directory of Open Access Journals (Sweden)

    Joshua Kuang-Chao Chen

    Full Text Available Previous animal study revealed that post-implantation electrical detection levels significantly declined within days. The impact of cochlear implant (CI insertion on human auditory pathway in terms of impedance and electrically evoked compound action potential (ECAP variation within hours after surgery remains unclear, since at this time frequency mapping can only commence weeks after implantation due to factors associated with wound conditions. The study presented our experiences with regards to initial switch-on within 24 hours, and thus the findings about the milieus inside cochlea within the first few hours after cochlear implantation in terms of impedance/ECAP fluctuations. The charts of fifty-four subjects with profound hearing impairment were studied. A minimal invasive approach was used for cochlear implantation, characterized by a small skin incision (≈ 2.5 cm and soft techniques for cochleostomy. Impedance/ECAP was measured intro-operatively and within 24 hours post-operatively. Initial mapping within 24 hours post-operatively was performed in all patients without major complications. Impedance/ECAP became significantly lower measured within 24 hours post-operatively as compared with intra-operatively (p<0.001. There were no differences between pre-operative and post-operative threshold for air-conduction hearing. A significant drop of impedance/ECAP in one day after cochlear implantation was revealed for the first time in human beings. Mechanisms could be related to the restoration of neuronal sensitivity to the electrical stimulation, and/or the interaction between the matrix enveloping the electrodes and the electrical stimulation of the initial switch-on. Less wound pain/swelling and soft techniques both contributed to the success of immediate initial mapping, which implied a stable micro-environment inside the cochlea despite electrodes insertion. Our research invites further studies to correlate initial impedance/ECAP changes

  5. A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

    Science.gov (United States)

    Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

    2016-12-01

    The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

  6. Cochlear Implantation in Siblings With Refsum's Disease.

    Science.gov (United States)

    Stähr, Kerstin; Kuechler, Alma; Gencik, Martin; Arnolds, Judith; Dendy, Meaghan; Lang, Stephan; Arweiler-Harbeck, Diana

    2017-08-01

    Whether the origin of severe hearing loss in Refsum's syndrome is caused by cochlear impairment or retrocochlear degeneration remains unclear. This case report aims to investigate hearing performance before and after cochlear implantation to shed light on this question. Also, identification of new mutations causing Refsum's syndrome would be helpful in generating additional means of diagnosis. A family of 4 individuals was subjected to genetic testing. Two siblings (56 and 61 years old) suffered from severe hearing and vision loss and received bilateral cochlear implants. Genetic analysis, audiological outcome, and clinical examinations were performed. One new mutation in the PHYH gene (c.768del63bp) causing Refsum's disease was found. Preoperative distortion product otoacoustic emissions (DPAOEs) were absent. Postoperative speech perception in Freiburger speech test was 100% for bisyllabic words and 85% (patient No. 1) and 65% (patient No. 2), respectively, for monosyllabic words. Five years after implantation, speech perception remained stable for bisyllabic words but showed decreasing capabilities for monosyllabic words. A new mutation causing Refsum's disease is presented. Cochlear implantation in case of severe hearing loss leads to an improvement in speech perception and should be recommended for patients with Refsum's disease, especially when the hearing loss is combined with a severe loss of vision. Decrease of speech perception in the long-term follow-up could indicate an additional retrocochlear degeneration.

  7. Libyan cochlear implant programme: achievements, difficulties, and ...

    African Journals Online (AJOL)

    Data relating to the patients who received cochlear implantation at Tripoli Medical Centre between October 2007 and February 2010 were analysed. Implant operations were performed on 37 patients. All patients received Med-El SONATATI100 devices. Thirty-four (91.9%) of these patients were children, whilst three (8.1%) ...

  8. Environmental Sound Training in Cochlear Implant Users

    Science.gov (United States)

    Shafiro, Valeriy; Sheft, Stanley; Kuvadia, Sejal; Gygi, Brian

    2015-01-01

    Purpose: The study investigated the effect of a short computer-based environmental sound training regimen on the perception of environmental sounds and speech in experienced cochlear implant (CI) patients. Method: Fourteen CI patients with the average of 5 years of CI experience participated. The protocol consisted of 2 pretests, 1 week apart,…

  9. Gender Categorization in Cochlear Implant Users

    Science.gov (United States)

    Massida, Zoe; Marx, Mathieu; Belin, Pascal; James, Christopher; Fraysse, Bernard; Barone, Pascal; Deguine, Olivier

    2013-01-01

    Purpose: In this study, the authors examined the ability of subjects with cochlear implants (CIs) to discriminate voice gender and how this ability evolved as a function of CI experience. Method: The authors presented a continuum of voice samples created by voice morphing, with 9 intermediate acoustic parameter steps between a typical male and a…

  10. Simplifying cochlear implant speech processor fitting

    NARCIS (Netherlands)

    Willeboer, C.

    2008-01-01

    Conventional fittings of the speech processor of a cochlear implant (CI) rely to a large extent on the implant recipient's subjective responses. For each of the 22 intracochlear electrodes the recipient has to indicate the threshold level (T-level) and comfortable loudness level (C-level) while

  11. The preoperative imaging evaluation for cochlear implantation

    International Nuclear Information System (INIS)

    Liu Zhonglin; Wang Zhenchang; Fu Lin; Li Yong; Xian Junfang; Yang Bentao; Lan Baosen; Li Yongxin; Zheng Jun; Song Yan; Liu Bo; Chen Xueqing; He Haili

    2006-01-01

    Objective: To analyze CT and MRI findings of temporal bone and to evaluate preoperative diagnostic value for cochlear implantation. Methods: One hundred and sixty candidates for cochlear implantation were examined with axial CT scan, 64 of them also with coronal CT scan, and 119 patients with MRI. Results: All of 320 ears were well-aerated, and 206 ears had mastoid cavities extended posteriorly to the sigmoid sinus. The length from posterior-lateral tympanic wall to the outer cortex was (2.34±0.42) mm (left side) and (2.25±0.40) mm (right side) (U=1.887, P 1 and T 2 signal on MRI. The congenital malformations of inner ear occurred in 67 ears, including complete dysplasia in 1 ear, cochlear hypodysplasia in 6 ears, Mondini deformation in 5 ears, enlarged vestibular aqueduct in 40 ears, dysplastic semicircular canal and the vestibulae in 10 ears, and narrowing of internal auditory canal in 5 ears. Conclusion: Preoperative imaging examinations can provide critical information to ensure successful cochlear' implantation. (authors)

  12. Listening Effort With Cochlear Implant Simulations

    NARCIS (Netherlands)

    Pals, Carina; Sarampalis, Anastasios; Başkent, Deniz

    2013-01-01

    Purpose: Fitting a cochlear implant (CI) for optimal speech perception does not necessarily optimize listening effort. This study aimed to show that listening effort may change between CI processing conditions for which speech intelligibility remains constant. Method: Nineteen normal-hearing

  13. Neurogenetic and morphogenetic heterogeneity in the bed nucleus of the stria terminalis

    International Nuclear Information System (INIS)

    Bayer, S.A.

    1987-01-01

    Neurogenesis and morphogenesis in the rat bed nucleus of the stria terminalis (strial bed nucleus) were examined with [ 3 H]thymidine autoradiography. For neurogenesis, the experimental animals were the offspring of pregnant females given an injection of [ 3 H]thymidine on 2 consecutive gestational days. Nine groups of embryos were exposed to [ 3 H]thymidine on E13-E14, E14-E15,... E21-E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24-hour periods were quantified at six anteroposterior levels in the strial bed nucleus. On the basis of neurogenetic gradients, the strial bed nucleus was divided into anterior and posterior parts. The anterior strial bed nucleus shows a caudal (older) to rostral (younger) neurogenetic gradient. Cells in the vicinity of the anterior commissural decussation are generated mainly between E13 and E16, cells just posterior to the nucleus accumbens mainly between E15 and E17. Within each rostrocaudal level, neurons originate in combined dorsal to ventral and medial to lateral neurogenetic gradients so that the oldest cells are located ventromedially and the youngest cells dorsolaterally. The most caudal level has some small neurons adjacent to the internal capsule that originate between E17 and E20. In the posterior strial bed nucleus, neurons extend ventromedially into the posterior preoptic area. Cells are generated simultaneously along the rostrocaudal plane in a modified lateral (older) to medial (younger) neurogenetic gradient. Ventrolateral neurons originate mainly between E13 and E16, dorsolateral neurons mainly between E15 and E16, and medial neurons mainly between E15 and E17. The youngest neurons are clumped into a medial core area just ventral to the fornix

  14. Laterodorsal nucleus of the thalamus: A processor of somatosensory inputs.

    Science.gov (United States)